Depression, a leading global health burden, involves neuroimmune dysregulation and neuroinflammation. As a promising non-pharmacological approach, acupuncture has been supported by numerous studies as an effective intervention for alleviating depression. The antidepressant mechanisms of acupuncture involve a multitarget modulation of neuroimmune crosstalk, such as restoring hypothalamic-pituitary-adrenal (HPA) axis homeostasis, inhibiting microglial and astrocytic activation, regulating autophagy, inhibiting key inflammatory signaling pathways, activating anti-inflammatory pathways via the vagus nerve, and rebalancing gut-brain axis communication by modifying microbiota. Integrating acupuncture with advanced neuromodulation techniques may enhance its effectiveness in treating depression. It needs further study to validate acupuncture as an effective therapeutic strategy in the field of neuroimmunology for depression. This review summarizes evidence elucidating how acupuncture regulates neuroimmune crosstalk in depression. It not only provides a scientific basis for its application but also advances the understanding of the pathophysiology of depression by highlighting the interplay between neuroimmune interaction and inflammatory pathways.

Background: Neuroinflammation lays a prominent impact in the pathophysiology of depression, and numerous studies have been conducted in recent decades. Bibliometric analysis is of important for understanding the hot spots and research trends in a certain subject field. However, no systematic bibliometric study exists in this field to date. The purpose of the study focused on the trends and hotspots in neuroinflammation of depression and provided future researchers with guidance and sights. Methods: Publications (2004-2023) were obtained from the WoSCC, and analyzed by HistCite, VOSviewer, CiteSpace, and Bibliometrix. The impact of publications was assessed by TGCS. Results: We analyzed 1,496 articles published in 409 journals and authored by 46,533 researchers across 72 countries and regions. The most prolific countries were China, the USA, and Brazil, and the most cited countries were the USA, followed with China and the UK, while the most prolific and cited institution was University Toronto (records=34, TGCS=2,137). Brain Behavior and Immunity is the leading journal that regularly published research in this field (records=93, TGCS=6,247). NLRP3 inflammasome, microglia, TNF-α, and brain-derived neurotrophic factor (BDNF) were the basis of neuroinflammation in depression. C-reactive protein, an important marker of inflammation, has been discussed for the longest time in this disease. In recent five years, two most frontier potential areas in studying depression were gut microbiota dysbiosis and BDNF. Conclusions: There remains a strong research basis for neuroinflammation in depression from this bibliometric analysis. Microglial activation, gut microbiota, cytokine signaling, and oxidative stress were research hotspots in recent years. In the future, chronic stress, hippocampal structure, and gut microbiota will continue to be studied in the field of neuroinflammation in depression. This study may benefit scientists in identifying potential directions for future study and providing clinicians with new ideas for treatment.

The glymphatic system is essential for maintaining fluid homeostasis and clearing metabolic waste in the brain. Existing evidence suggests that this system is disrupted by systemic inflammation; however, the pathological characteristics and mechanisms underlying this disruption remain unclear. Near-infrared II imaging reveals an excessive increase in perivascular cerebrospinal fluid (CSF) influx and a reduction in CSF efflux, accompanied by impaired glymphatic clearance within 72 h in mice intraperitoneally injected with lipopolysaccharide (LPS) at a dose of 5 mg kg-1, which does not significantly disrupt the blood-brain barrier. An inverse relationship is observed between cerebral blood flow (CBF) and glymphatic influx trends following LPS challenge. Enhancement of CBF via levosimendan effectively ameliorates glymphatic flux and clearance, but these improvements are abolished by bilateral carotid artery stenosis surgery, indicating that cerebral hypoperfusion mediates LPS-induced glymphatic dysfunction. Furthermore, levosimendan administration attenuates LPS-induced neuroinflammation and neurological deficits. Mechanistically, CBF augmentation prevents the LPS-induced perivascular Aquaporin-4 (AQP4) depolarization, whereas the AQP4 inhibitor TGN-020 blocks its beneficial effects on both amyloid-β clearance and neuroinflammation suppression, confirming AQP4's pivotal role. Behaviorally, levosimendan ameliorates LPS-induced neurological deficits. These findings establish cerebral hypoperfusion as a key mediator of systemic inflammation-induced glymphatic dysfunction, revealing a promising therapeutic avenue for sepsis-associated encephalopathy.

Objective To observe the effect of manual acupuncture stimulation on changes of behavior and hippocampal signaling pathways of AMP-activated kinase(AMPK)/UNC-51-like kinase 1(ULK1)in rats with chronic unpredictable mild stress(CUMS)-induced depression,so as to explore its molecular mechanism underlying improvement of depression.Methods Thirty-two male SD rats were randomly divided into normal control,model,acupuncture and medication(fluoxetine)groups,with 8 rats in each group.The depression model was established by using CUMS(fasting,water depredation,restraint,swimming in cold water,crowding,stroboscope stimulation,and tail clipping,each of which was used once a week)for 6 weeks.Manual acupuncture stimulation was applied to"Baihui"(GV20)and"Yintang"(EX-HN3)for 10 min,once daily,6 times a week for 6 weeks before every-day modeling.Rats of the medication group received gavage of fluoxetine(10 mg/kg)once a day for 6 weeks before every-day modeling.The percentage of sucrose preference,and the percentages of open arm times and open arm time in the elevated plus maze experiments were detected.The expression levels of AMPK,phosphorylated(p)-AMPK,ULK1,p-ULK1,mammalian target of rapamycin(mTOR)and p-mTOR proteins in the hippocampus tissue were detected by Western blot,and the expression of autophagy effecting protein(Beclin-1)and the selective autophagy receptors(p62)mRNA in the hippocampal tissue was detected using real-time fluorescence quantitative PCR,respectively.Results Compared with the normal group,the percentage of sucrose preference,percentage of times of entering the open arm and percentage of open arm time,the expression levels of p-AMPK/AMPK ratio,p-ULK1/ULK1 ratio of proteins,and Beclin-1 mRNA were significantly decreased(P<0.01,P<0.05),and the expression levels of p-mTOR/mTOR ratio and p62 mRNA were significantly increased(P<0.01,P<0.05)in the model group.In comparison with the model group,the percentage of sucrose preference,percentage of open arm times and open arm time,the expression levels of p-AMPK/AMPK ratio,p-ULK1/ULK1 ratio of proteins,and Beclin-1 mRNA were significantly increased in both acupuncture and medication groups(P<0.01,P<0.05),while the expression levels of p-mTOR/mTOR ratio of proteins,and p62 mRNA were markedly decreased only in the medication group(P<0.05).Conclusion Acupuncture treatment can alleviate depression-like behavior in CUMS rats,which may be related to its functions in up-regulating AMPK/ULK1 signaling pathway to induce cellular autophagy in the hippocampus.

Background Acupuncture plays a critical role for the treatment of patients with Parkinson's disease (PD), which is characterized by ferroptosis of dopaminergic neurons. It has been found that acupuncture can reduce iron accumulation. However, the mechanism of acupuncture therapy against PD by inhibiting ferroptosis remains unclear. Objectives To investigate the potential mechanism of acupuncture on alleviating ferroptosis in 6-OHDA-induced PD rats. Methods Male Sprague-Dawley rats were randomly divided into sham group, acupuncture group, and PD model group, with the PD model induced by 6-OHDA. The motor function of the rats was tested by the rotation test and suspension test, respectively. Immunohistochemistry and iron staining were performed to analyze nerve damage, and the effect of acupuncture on the accumulation of iron in the substantia nigra (SN). RNA-seq analysis in the SN of rats were performed to discover ferroptosis-related genes. Differentially expressed genes (DEGs) resulted from the acupuncture treatment were identified and were used for Gene Ontology (GO) function, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A protein–protein interaction (PPI) network was constructed, and alternative splicing (AS) analysis of the transcriptome was performed. Western Blot was used to detect the protein level change of Slc7a11/xCT. Results Rotation test and suspension test indicated a positive effect of acupuncture on body weight gain and limb function. Perl's iron staining and ELISA test detected 6-OHDA induced iron accumulation in the SN and nerve damage, which was mitigated by acupuncture treatment. Acupuncture treatment brought about the differential expression of a total of 1088 genes in the SN of rats. GO and KEGG enrichment revealed that such DEGs were mainly associated with several key biological process (BP), cellular component (CC) and molecular function (MF) terms. These terms included collagen fibril organization, extracellular matrix organization, collagen trimer, extracellular matrix components, chemokine receptor binding and cargo receptor activity, etc. Additionally, the DEGs were found to be involved in pathways such as complement and coagulation. The PPI network of DEGs suggested a critical role of Slc7a11, which was further supported by an up-regulated Slc7a11/xCT protein level in the substantia nigra (SN) tissue of rats treated with acupuncture compared to their PD model counterparts (P=0.045). Conclusion Acupuncture may prevent ferroptosis through Slc7a11/xCT as one of the targets in 6-OHDA-induced PD model and thereby could be promising for PD treatment.

OBJECTIVETo observe the effect of acupuncture on the protein kinase R-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2α (eIF2α) signaling pathway in the hippocampus of rats with post-traumatic stress disorder (PTSD), so as to explore the underlying mechanism of acupuncture in treating PTSD.METHODSTwenty-eight SD rats were randomly divided into normal, model, acupuncture and sertraline groups, with 7 rats in each group. The PTSD model was established by single prolonged stress method. The next day after modeling, acupuncture was applied to "Baihui" (GV20) and "Dazhui" (GV14) of rats in the acupuncture group for 10 min, once a day for 7 days. Sertraline (10 mg/kg) was given by gavage to rats of the sertraline group daily for 7 days. The behavioral changes of rats were detected by elevated cross maze experiment and new object recognition experiment. The expression levels of PERK,phosphorylated(p)-PERK, eIF2α, p-eIF2α and activating transcription factor 4 (ATF4) proteins in hippocampus were detected by Western blot. The ultrastructure of hippocampal neurons was observed by transmission electron microscopy.RESULTSCompared with the normal group, the percentage of times and retention time of entering the open arm of the elevated cross maze experiment, and new object recognition index were significantly decreased (P<0.01); the expression levels of p-PERK, p-eIF2α and ATF4 proteins in hippocampus were significantly increased (P<0.05) of rats in the model group. Compared with the model group, the percentage of times and retention time of entering the open arm, and new object recognition index were significantly increased (P<0.05，P<0.01), the expression levels of p-PERK, p-eIF2α and ATF4 proteins in hippocampus were significantly decreased (P<0.05, P<0.01) of rats in the acupuncture and sertraline groups; the expression level of eIF2α protein was significantly decreased (P<0.05) in the sertraline group. Hippocampal neurons in the model group were damaged, the rough endoplasmic reticulum showed severe dilation, the mitochondrial cristae showed reduction or mild cavitation; compared with the model group, hippocampal neurons structural damage and the rough endoplasmic reticulum dilation were alleviated， and only some of the mitochondrial cristae decreased in the acupuncture and sertraline groups.CONCLUSIONAcupuncture can alleviate the anxiety behavior as well as the recognition and memory ability of PTSD rats, and its mechanism may be related to the inhibition of hippocampus PERK/eIF2α signaling pathway and the reduction of hippocampal neuron damage caused by endoplasmic reticulum stress.

Ischemic brain injury is a severe medical condition with high incidences in elderly people without effective treatment for the resulting neural damages. Using a unilateral mouse stroke model, we analyze single-cell transcriptomes of ipsilateral and contralateral cortical penumbra regions to objectively reveal molecular events with single-cell resolution at 4 h and 1, 3, and 7 days post-injury. Here, we report that neurons are among the first cells that sense the lack of blood supplies by elevated expression of CCAAT/enhancer-bind-ing protein 0 (C/EBP0). To our surprise, the canonical inflammatory cytokine gene targets for C/EBP0, including interleukin-10 (IL-10) and tumor necrosis factor a (TNF-a), are subsequently induced also in neuronal cells. Neuronal-specific silencing of C/EBP0 or IL-10 and TNF-a substantially alleviates down-stream inflammatory injury responses and is profoundly neural protective. Taken together, our findings reveal a neuronal inflammatory mechanism underlying early pathological triggers of ischemic brain injury.

Objective To inquire into the mechanism of acupuncture in the treatment of depression.Methods Sprague-Dawley rats were randomly divided into the normal group, the model group, the acupuncture group, and the fluoxetine group（n=8 rats in each）. The depression model was established by using chronic unpredictable mild stress method. The “Baihui”（GV20） and “Yintang”（GV29） acupoints were selected in the acupuncture group. Acupuncture treatment was given before modeling each day, with needle retention for 10 minutes, six times a week. Fluoxetine was given intragastrically before modeling each day（10 mg/kg）, once daily. The behavior tests, including the body weight and the sucrose preference test were performed. The hippocampal protein expression levels of NLRP3, ASC, and Caspase-1 were measured by Western blotting. The hippocampal gene expression levels of IL-1β and IL-18 were measured by real-time fluorescent quantitative PCR. The hippocampal contents of IL-1β, IL-18, IL-4, and IL-10 were measured by ELISA.Results Compared with the normal group, the body weight and the percentage of sucrose preference test were decreased in the model group（P＜0.05, P＜0.01）, the hippocampal expression levels of NLRP3, ASC, and Caspase-1 were increased（P＜0.01）, the hippocampal gene expression of the pro-inflammatory factors IL-1β and IL-18 were increased（P＜0.01, P＜0.05）, and the protein levels of IL-1β and IL-18 in the hippocampus were increased（P＜0.01, P＜0.05）, and the levels of anti-inflammatory factors IL-4 and IL-10 were decreased（P＜0.01, P＜0.05）. Compared with the model group, there was no statistical difference in the body weight in the acupuncture and fluoxetine groups（P ＞ 0.05）, while the percentage of sucrose preference was increased in both the acupuncture and fluoxetine groups（P＜0.05）. Compared with the model group, the expression levels of hippocampal NLRP3, ASC, and Caspase-1 were decreased（P＜0.01）, the gene expression levels of the pro-inflammatory factors IL-1β and IL-18（P＜0.01,P＜0.05） and the protein levels of IL-1β and IL-18 were reduced（P＜0.01, P＜0.05）, and the content of the anti-inflammatory factor IL-10 in the hippocampus was increased（P＜0.05）. However, there was no statistical difference in the content of IL-4（P＞0.05）. In addition, there was no statistical difference between the acupuncture and fluoxetine groups（P＞0.05）.Conclusion Acupuncture treatment could alleviate depressive behavior and exert antidepressant effects, possibly by inhibiting the NLRP3 inflammasome activity and the related inflammatory response, reducing pro-inflammatory cytokine levels, and increasing anti-inflammatory cytokine levels in the hippocampus.

Background. Most patients with drug-resistant epilepsy (DRE) have cognitive impairment and sleep disturbance. There was a significant correlation between sleep disorders and cognitive dysfunction. This study performed surgical treatment on patients with DRE and observed seizures, sleep, and cognition in patients with DRE in 6th month after operation to clarify the correlation between sleep and cognition in DRE patients.Methods. 21 individuals with DRE were recruited to enroll in this trial. Each participant completed epileptic focus resection. Seizure frequency was the principle index; the mean seizure frequency was 1 month before surgery and six months after surgery. Cognitive function was assessed by MMSE, and sleep status was assessed by PSQI and ActiGraph; assessments were performed before and 6 months after surgery. Results. There were significant differences between conditions on all outcome measures; after 6 months of surgery, compared with before treatment, the monthly average seizure frequency of DRE decreased, which was statistically significant (P<0.001) compared with that before treatment. The MMSE score of DRE patients was significantly higher than before (P<0.01), especially the ability of attention, calculation, and recall in MMSE score, which was significantly higher than before operation (respectively, P<0.001 and P<0.01). The subjective sleep evaluation index PSQI and objective measurement of sleep latency, total sleep time, and sleep efficiency of patients with DRE by ActiGraph were statistically significant (respectively, P<0.01) compared with that before treatment. There was a correlation between seizure frequency and MMSE (r=−0.8887, P<0.0001), PSQI (0.5515, P<0.01), sleep latency (0.5353, P<0.05), total sleep time (-0.7814, P<0.0001), and sleep efficiency (-0.4380, P<0.05). Conclusions. Surgery can effectively reduce the epileptic seizures frequency in patients with DRE and indirectly improve the computational power, attention, recall ability, and sleep status of patients. However, this result did not show a correlation between improved cognitive function and sleep, so the patient’s cognitive function may be caused by surgery to improve the frequency of seizures. So, whether the improvement of patients’ sleep conditions can also significantly improve the frequency of attacks and cognitive function in patients with DRE needs further exploration.

OBJECTIVE:To observe the effect of acupuncture on endoplasmic reticulum stress-related molecules glucose regulated protein 78 kD (GRP78), C/EBP homologous protein (CHOP), cysteinyl aspartate specific proteinase-12 (Caspase-12) and cysteinyl aspartate specific proteinase-3 (Caspase-3)in the hippocampus of rats with post-traumatic stress disorder, so as to explore the possible mechanism of acupuncture in treating post-traumatic stress disorder (PTSD).METHODS:Twenty-eight SD rats were randomly divided into normal control, model, acupuncture and sertraline groups, with 7 rats in each group. The PTSD rat model was established by single prolonged stress. After modeling, acupuncture was applied to "Baihui" (GV20) and "Dazhui" (GV14) for rats of the acupuncture group for 10 min, once a day for 7 days. Sertraline (10 mg/kg) was given by gavage to rats of the sertraline group daily for 7 days. Rats' behavior was assessed by open field test and novelty-suppressed test. The mRNA expression levels of GRP78 and CHOP in the hippocampus were detected by real-time PCR. The expression le-vels of Caspase-12 and Caspase-3 in the hippocampus were detected by Western blot.RESULTS:Compared with the normal control group, the rearing and crossing times were decreased (P<0.05), the time remaining in the central zone and the total distance of movement were significantly reduced (P<0.01, P<0.05), the time of entering the central area for the first time was significantly increased (P<0.01), the latency of the novelty-suppressed feeding was significantly increased (P<0.05) in the model group, meanwhile the expression level of GRP78 and CHOP mRNAs, Caspase-12 and Caspase-3 proteins in the hippocampus were increased (P<0.05, P<0.01). In comparison with the model group, the crossing times, the time remaining in the central zone and total distance of movement were increased significantly (P<0.05, P<0.01), while the time of entering the central area for the first time, the expression levels of GRP78 and CHOP mRNAs, and Caspase-12 protein in the hippocampus were obviously decreased (P<0.05, P<0.01) in the acupuncture and sertraline groups. In addition, the rearing times were increased significantly (P<0.05), the latency of the novelty-suppressed feeding and the expression of Caspase-3 were decreased significantly (P<0.05) in the sertraline group than in the model group.CONCLUSION:Acupuncture can significantly down-regulate the expression of endoplasmic reticulum stress-related molecules GRP78, CHOP and Caspase-12 in PTSD rats, which may be one of the mechanisms of acupuncture in treating PTSD.

Hepatocellular carcinoma (HCC) is an often-fatal malignant tumor with high lethality. Despite advances and significant efficacy in monotherapy, cancer therapy continues to pose several challenges. Novel combination regimens are an emerging strategy for anti-HCC and have demonstrated to be effective. Here, we propose a potential combination for HCC treatment named arsenic trioxide cooperate cryptotanshinone (ACCS). A remarkable synergistic therapeutic effect has been achieved compared with drugs alone in both in vivo and in vitro experiments. Mechanism study indicated that ACCS exerts its therapeutic actions by regulating macrophage-related immunity and glycolysis. ACCS potentiates the polarization of M1 macrophages and elevates the proportion of M1/M2 to remodel tumor immunity. Further molecular mechanism study revealed that ACCS intensifies the glucose utilization and glycolysis in the macrophage by increasing the phosphorylation of AMPK to activating the AMPK singling pathway. In conclusion, ACCS is a highly potential combination regimen for HCC treatment. The therapeutic potential of ACCS as a candidate option for anticancer drugs in restoring the balance of immunity and metabolism deserves further investigation.

OBJECTIVE:To observe the effect of acupuncture on the expression of proinflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), microglia marker ion calcium adaptor protein (Iba-1) and triggering receptor expressed on myeloid cells 2 (TREM2) in the prefrontal cortex of chronic stress-induced depression rats, so as to explore its antidepressant mechanism.METHODS:Thirty-two SD rats were randomly divided into normal control, model, acupuncture and fluoxetine groups, with 8 rats in each group. The depression model was established by using chronic mild unpredictable stress methods for 6 weeks. Manual acupuncture stimulation was applied to "Baihui" (GV20) and "Yintang" (GV29) for 10 min before modeling for 6 weeks. Fluoxetine (10 mg/kg, 1 mg/mL) was given to rats of the fluoxetine group by gavage before stress stimulation, once every day for 6 weeks. The open field test was used to evaluate the behavioral changes of rats. The contents of IL-1β, IL-6 in the prefrontal cortex were determined by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to determine the expression of Iba-1 in the prefrontal cortex. The TREM2 gene expression in the prefrontal cortex was determined by real time fluorescent quantitative polymerase chain reaction (RT-PCR).RESULTS:After modeling, the crossing numbers and rearing times were significantly decreased in the model group relevant to the control group (P<0.05). After the treatment, the crossing numbers were significantly increased in the acupuncture and fluoxetine groups (P<0.05), while the rearing times in the acupuncture group were significantly increased (P<0.05). Compared with the control group, the contents of IL-1β, IL-6 and the expression of Iba-1 positive cells in the prefrontal cortex were significantly increased in the model group (P<0.05), while the expression of TREM2 gene in the prefrontal cortex was significantly decreased (P<0.05). After the treatment, the increased levels of IL-1β, IL-6 and Iba-1 positive cells and the decreased TREM2 gene expression were considerably reversed in both acupuncture and fluoxetine groups compared with the model group (P<0.05).CONCLUSION:Acupuncture intervention plays a positive role in anti-depression in rats, which may be related to its effects in inhibiting the activation of microglia, reducing the expression of proinflammatory cytokines, and increasing TREM2 expression in the prefrontal cortex.

Ethnopharmacological relevance: Chaihu-Longgu-Muli Decoction (CLMD) is a classic prescription created by Zhong-jing Zhang, a famous ancient Chinese medical scientist, to harmonize uncontrollable body activities and calm the minds. Now Traditional Chinese Medicine (TCM) physicians often apply it to treat psychiatric diseases such as epilepsy. Aim of the study: This study investigated the mechanism of the effect of Chaihu-Longgu-Muli Decoction (CLMD) on hippocampal neurons pyroptosis in rats with Temporal Lobe Epilepsy (TLE). Materials and methods: The lithium chloride-pilocarpine-induced TLE rat model was established. The behavioral testing was performed and, the expression of IL-1 beta and TNF-alpha in serum was detected by ELISA, qRT-PCR was used to detect the mRNA expression of NLRP3, Caspase-1, IL-1 beta and TNF-alpha in hippocampus. The expression of NLRP3 and Caspase-1 in hippocampal dentate gyrus was detected by immunofluorescence assay. Results: CLMD could significantly suppress the frequency and duration time of epileptic seizures, reduce the expression of NLRP3, Caspase-1 TNF-alpha and IL-1 beta. Conclusions: CLMD exerted an obvious antiepileptic effect by improving pyroptosis in hippocampal neurons of TLE rats.

The Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-driven inflammatory response plays a key role in the pathophysiology of depression. Mounting evidence suggests that acupuncture is an effective treatment for depression. In this study, we investigated the effects of acupuncture treatment at the acupoints Baihui (GV20) and Yintang (GV29) on NLRP3 inflammasome in the prefrontal cortex (PFC) of an animal model of depression. Rats that underwent chronic unpredictable mild stress (CUMS) for 6 weeks showed depressive-like behaviors, which were confirmed by sucrose preference and locomotor activity in the open field test. The protein levels of NLRP3, apoptotic speck-containing protein with a card (ASC), and cysteinyl aspartate specific proteinase-1 (Caspase-1) in the PFC were detected by Western blot analysis. The mRNA and protein expressions of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in the PFC were measured by the real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Our results showed that the depressive-like behaviors in stressed rats were reversed by acupuncture treatment. Compared with control rats, the protein expression of NLRP3, ASC, and Caspase-1 and the mRNA and protein expressions of IL-1β and IL-18 in the PFC were markedly increased in CUMS rats. Acupuncture treatment significantly decreased the levels of NLRP3 inflammasome components and inflammatory cytokines in the PFC. Acupuncture treatment also reduced the number of TUNEL-positive cells in the PFC. These results suggested that acupuncture has antidepressant-like effects, and its mechanism appears to be involved in the inhibition of NLRP3 inflammasome activation and apoptosis in the PFC.

Post-traumatic stress disorder (PTSD) is a kind of chronic mental disorder after severe traumatic events. In this paper, the author reviewed the development of clinical and mechanism research of acupuncture and moxibustion for treating PTSD in the past 5 years. Clinical studies have shown that acupuncture could alleviate the symptoms of PTSD, and is an effective therapy for PTSD. The underlying mechanisms may include regulating neural circuit, neurotransmitters and receptors expression, signal pathway, apoptosis, immune cytokines and endocannabinoid system, et al. It could provide scientific basis of acupuncture and moxibustion for treating PTSD, and provide references for further study.

目的 研究蒙医温针治疗过程中iNOS信号通路对氧化应激及细胞因子的表达影响.方法 将SD大鼠随机分为正常组、对照组、模型组和温针组,力竭游泳3周造模.Morris水迷宫评估大鼠学习记忆能力、疲劳情况;ELISA检测海马和下丘脑IL-1β、IL-6、TNF-α及iNOS的含量.结果 Morris水迷实验,与模型组比温针组平均速度明显增高(P＜0.05),潜伏期时间减少(P＜0.05);疲劳模型大鼠海马和下丘脑IL-1β、IL-6、TNF-α及iNOS含量明显升高(P＜0.05),温针组海马和下丘脑IL-1β、TNF-α及iNOS及海马IL-6含量明显降低(P＜0.05).结论 慢性疲劳综合征可能涉及海马和下丘脑过度的炎症反应和潜在的炎症损伤;蒙医温针可减轻炎症反应的损害,具有抗炎作用.蒙医温针的疗效可能是通过抑制iNOS信号通路、增强抗氧化应激能力,改善认知功能障碍的.

OBJECTIVE:To observe the effect of moxibustion at "Zusanli"(ST36) on peripheral and central IL-6, IL-10 and IL-10/IL-6 changes in fatigue rats, so as to explore its mechanisms underlying relief of fatigue. METHODS:Twenty-one male SD rats were randomly divided into normal control, model and moxibustion groups with 7 rats in each group. The fatigue model was induced by exhausted weight-loaded swimming, once daily for 21 days. Moxibustion was applied to bilateral ST36 once every other day, for successive 11 times. The overall state and the body weight were observed. The levels of IL-6 and IL-10 in the serum, gastrocnemius and frontal cortex tissues were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS:Compared with the normal group, the body weight was significantly reduced on the 7th, 14th, and 21st day in the model group (P<0.05), and considerably increased on the 14th and 21st day in the moxibustion group relevant to the model group (P<0.05). After modeling, the levels of IL-6 in the serum, gastrocnemius and frontal cortex were significantly increased (P<0.05, P<0.01), while those of IL-10 was obviously decreased (P<0.05, P<0.01) in the model group relevant to the normal group, and ratio of IL-10/IL-6 was obviously decreased in the serum and frontal cortex of the model group relevant to the normal group (P<0.01). After the moxibustion intervention, the levels of IL-10 in the serum and frontal cortex were significantly increased (P<0.05), and ratio of IL-10/IL-6 in the serum and frontal cortex was significantly increased (P<0.01), while the IL-6 contents in the gastrocnemius and frontal cortex were notably decreased in the moxibustion group relevant to the model group (P<0.05). CONCLUSION:Moxibustion can inhibit weight-loaded swimming induced decrease of body weight in fatigue rats, which may be associated with its effects in balancing the levels of peripheral and central pro-inflammatory cytokine IL-6 and anti-inflammatory cytokine IL-10.

The inducible nitric oxide synthase/nitric oxide (iNOS/NO) signaling pathway and inflammatory cytokines play important roles in the pathogenesis of exercise-induced fatigue. Studies have found that Mongolian warm acupuncture (WA) could alleviate exercise-induced fatigue. However, the exact mechanisms underlying its effects remain unclear. In the present study, we investigated the effects of Mongolian WA on iNOS/NO signaling pathway and proinflammatory cytokines in a chronic exhaustive swimming induced fatigue rat model. Animals were randomly divided into Control group, Ctrl+WA group, Model group and Model+WA group. The body weight, exhaustive swimming time test, and Morris water maze test were performed before and after the chronic exhaustive swimming. The serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and iNOS were detected by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of IL-1β, IL-6, TNF-α, IFN-γ and iNOS in the hippocampus were measured by real-time polymerase chain reaction (RT-PCR). Moreover, the protein expression of iNOS in the hippocampus was measured by western-blot and the NO productions in the serum and hippocampus were detected by Griess reaction system. Chronic exhaustive exercise significantly reduced the body weight and exhaustive swimming time, and induced impairment in learning and memory, and which were reversed by WA treatment. Chronic exhaustive exercise also increased the expressions of iNOS and proinflammatory cytokines, while WA treatment significantly decreased the level of iNOS and proinflammatory cytokines. However, chronic exhaustive exercise did not affect the NO production. These findings demonstrated that WA could alleviate the chronic exhaustive swimming-induced fatigue and improve the learning and memory ability, and the actions might be related to the reduction of inflammatory response and iNOS expression.

OBJECTIVE:To observe the effect of moxibustion on interleukin-6(IL-6)/signal transduction and transcriptional activator 3(STAT3) signaling pathway in the frontal cortex of fatigue rats, so as to reveal its mechanisms underlying alleviation of fatigue. METHODS:Twenty-one male SD rats were randomly divided into normal control, model, and moxibustion groups (n＝7 rats in each group). The fatigue model was established by forcing the rats to have an exhausted swim under load condition, once daily for 21 days. Moxibustion was applied to bilateral "Zusanli"(ST36) for about 15 min, once every other day for 21 days. The level of IL-6 in the frontal cortex was detected by ELISA, and the expression of Janus kinase 2 (JAK2), phosphorylated JAK2 (p-JAK2), signal transduction and transcriptional activator 3(STAT3) and phosphorylated STAT3 (p-STAT3) proteins in the frontal cortex was detected by Western blot. RESULTS:After modeling, the levels of IL-6 content and p-STAT3 protein expression and ratio of p-STAT3/STAT3 were significantly increased in the model group relevant to the normal control group (P<0.01). Follo-wing moxibustion, the duration of load swimming on the 21st day was significantly prolonged (P<0.01), content of IL-6 and levels of p-STAT3 protein expression and ratio of p-STAT3/STAT3 were significantly down-regulated in the moxibustion group compared with the model group (P<0.05). No significant differences were found between the model and control, and between moxibustion and model groups in the expression levels of JAK2, p-JAK2, STAT3 and p-JAK2/JAK2 (P>0.05). CONCLUSION:Moxibustion intervention can relieve fatigue in fatigue rats, which is associated with its function in inhibiting IL-6/STAT3 signaling pathway to reduce inflammatory injury.

目的:研究砭贴或揿针百会与内关对模拟高原环境下大鼠脑组织损伤预防作用及其与血清炎性因子及脑组织血管内皮生长因子(VEGF)表达的关系.方法:45只雄性SD大鼠随机分为正常(A)组、模型(B)组、砭贴(C)组、揿针(D)组、药物(E)组,每组各9只.A组正常饲养,B组于百会、内关粘贴胶带,C组于百会、内关粘贴砭贴,D组于百会、内关刺入揿针,E组采用红景天提取物0.45g/kg灌胃.连续处理1周后,除A组均置于低压低氧环境下,24h后处死,HE染色鉴定脑组织形态,ELISA检测血清TNF-α、IL-6、IL-1 β蛋白表达,RT-qPCR检测脑组织VEGF mRNA表达.结果:与A组比较,B组大鼠脑组织损伤明显,血清TNF-α、脑组织VEGFmRNA表达显著升高(P＜0.05);与B组比较,C、D组大鼠脑组织损伤轻,血清TNF-o、脑组织VEGF表达显著降低(P＜0.05).结论:砭贴或揿针百会与内关可抑制高原环境大鼠脑损伤,可能与抑制血清TNF-α及脑组织VEGF表达相关.