Acupuncture treatment for ischemic stroke is characterized by multi-target and multi-pathway effects, involving various pathological processes of stroke. This article discusses the mechanisms of acupuncture in treating ischemic stroke from the perspectives of inflammatory response, programmed cell death (apoptosis, autophagy, ferroptosis, pyroptosis), oxidative stress, angiogenesis, and synaptic plasticity, aiming to provide insights and suggestions for future research.
Mistletoe (Viscum coloratum (Komar.) Nakai) is a parasitic plant with medicinal and culinary uses, yet its parasitic mechanisms on host species are largely unexplored. In this study, we performed an integrated transcriptomic and metabolomic analysis of mistletoe branches and leaves parasitizing on Tilia amurensis Rupr., Ulmus pumila L., and Populus ussuriensis Kom., investigating the potential molecular and metabolic mechanisms of mistletoe influenced by these hosts. Our results revealed notable differences in the transcriptional information of mistletoe branches and leaves across various host species, which was also reflected in their metabolic profiles. At the transcriptional level, lipid metabolism, carbohydrate metabolism and amino acid metabolism were the main pathway influenced by various hosts. Flavonoids and lipids were the primary differential components in the metabolic profile of mistletoe. Combined metabolomic and transcriptomic analyses demonstrated that glycerophospholipid metabolism comprising lipids, was a vital pathway for the activities of mistletoe parasites on their hosts. In this pathway, most metabolites, such as LysoPC, and the majority of genes, such as LYPLA2 and DPP1, exhibited the highest expression levels in Tilia amurensis Rupr. Mistletoe parasitizing Tilia amurensis Rupr., whether on branches or leaves, exhibited very significant differences compared to those parasitizing Ulmus pumila L. and Populus ussuriensis Kom. The findings provide key insights into the molecular mechanisms of mistletoe’s parasitic activities and how different hosts affect its transcriptional and metabolic profiles.
A simple and reliable method was developed to simultaneously monitor the residues of benzo[a]pyrene (BaP), benzo[b]fluoranthene (BbF) and chrysene (Chr) in Radix isatidis using a dispersive solid phase extraction technique (d-SPE). In this method, these polycyclic aromatic hydrocarbons (PAHs) were extracted and concentrated by zirconium (IV)-based UiO-67 material and analysed by ultra-high performance liquid chromatography with fluorescence detection (UHPLC-FLD). Key parameters of d-SPE were optimised to improve extraction efficiency. Under the optimised conditions, the method demonstrated good linearity, with limits of detection (LODs) ranging from 0.01 to 0.07 ng/g and limits of quantification (LOQs) from 0.04 to 0.18 ng/g. The developed method was applied to determine trace PAHs in complex matrices, yielding recoveries ranging from 80.00 % to 114.6% for Radix isatidis samples. The precisions of intra-day and inter-day were 1.10-8.70% and 3.90-12.8%, respectively. The enrichment factor (EF) values for the tested analytes varied from 2.42 to 3.47. The absolute recoveries (ARs %) were between 80.80 %and 115.7 %. The proposed method proved to be efficient and reliable for detecting trace PAHs in Radix isatidis and holds great promise for monitoring trace PAHs in other complex food matrices.
Litchi, valued for its vibrant appearance and nutritional content, undergoes rapid browning of the pericarp (PE), reducing its market value. However, the browning mechanism and the impact of browning on the pulp (PU) are not fully understood. This study, litchi fruits were considered at five browning stages. Untargeted LC-MS metabolomics and cluster analysis revealed more pronounced browning-related metabolic changes in the PE than in the PU, as shown by greater separation in PE via principal component analysis. Overall, 53 differential metabolites in PE and 24 in PU were characterized, including flavonoids and lipids. The correlation analysis results revealed that the metabolites strongly associated with the browning process in the PE were primarily lipid compounds. Pathway analysis indicated that PE browning was associated with flavonoid pathway and lipid metabolism. These findings offered insights into litchi browning metabolism and a basis for improving PE browning delay and post-harvest preservation.
Background:Almost all elderly individuals will encounter varying degrees of trouble caused by intervertebral disc degeneration. As a common degenerative spinal disorder, the harm of lumbar disc herniation (LDH) depends on the location of the nucleus pulposus herniation. However, population studies on the mechanisms of disc herniation at different levels are limited. Therefore, we conducted comparative analyses of serum metabolic characteristics in LDH patients with disc herniation at different locations. Methods:In this study, 110 LDH patients (59 patients with L4-L5 protrusion site and 51 patients with L4-L5 protrusion site) were collected from June 2nd to October 1st, 2023 in Wuhan City, China. Untargeted metabolomics analysis based on ultra-high-pressure liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-QTOF-MS/MS) was analyzed the serum metabolic characteristics. Results:As a result of principal component analysis (PCA) analysis, there was a clear separation trend in the metabolic profiles between L4-L5 and L5-S1 LDH patients in males, but not in females. Further, 28 metabolites with significant changes were screened in males with L4-L5 disc herniation compared to males with L5-S1 disc herniation. Among them, 25 metabolites were involved in glycerophospholipid metabolism, sphingolipid metabolism and tryptophan metabolism. Conclusion:These findings demonstrate gender-specific differences in LDH patients. Moreover, the location-specific metabolic signatures in males were uncovered. This study could provide new insights into the gender-specific degenerative mechanisms associated with lesions in different locations, and inform targeted rehabilitation strategies for managing LDH.
Research on dark tea-derived exosome-like nanoparticles (TELNs) and microbial fermentation-mediated modifications of TELNs remains limited. To comprehensively explore the fermentation-induced alterations in TELNs' physical properties, metabolic composition, and biological functions, a systematic investigation was conducted in this study. Particle size distribution, zeta potential, protein content, and particle concentration of TELNs were characterized and compared before and after Aspergillus cristatus (AC) fermentation using nanoparticle tracking analysis (NTA), dynamic light scattering (DLS), and bicinchoninic acid assay (BCA), respectively. Untargeted metabolomics was employed to profile metabolic changes, while functional assessment was performed in a non-alcoholic fatty liver disease (NAFLD) mouse model. As a result, AC fermentation significantly reduced the particle size of TELNs and increased their yield. It altered the overall metabolite profile of TELNs, and a total of 30 differential metabolites were tentatively identified, mainly including flavonoids, alkaloids, and lipids. Meanwhile, AC fermentation enhanced the blood-lipid-lowering and anti-inflammatory abilities of TELNs in NAFLD mice. This study deepened the understanding of the molecular-level changes during tea fermentation, and offered a new perspective on the applications of dark tea or TELNs in the fields of food science and medical healthcare.
Osteoarthritis (OA) is prevalent, yet its management remains challenging. This meta-analysis aims to evaluate the efficacy of acupuncture combined with moxibustion versus other standard treatments in patients with knee osteoarthritis (KOA) based on randomized controlled trials (RCTs). Searches were conducted in Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to retrieve relevant RCTs. Data on baseline characteristics, treatment efficacy, and adverse events were extracted. The analysis utilized pooled weighted mean differences (WMD) and risk ratios (RR) with 95
Pericarpium Citri Reticulatae is susceptible to mycotoxin contamination under improper processing or storage conditions, necessitating reliable analytical methods for its monitoring. However, there was a lack of a reliable method that can quantify zearalenone (ZEN) and its major metabolites simultaneously in the Pericarpium Citri Reticulatae matrix. To address this gap, this work, for the first time, developed and validated a method based on immunoaffinity column purification coupled with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the simultaneous determination of ZEN and its five metabolites in Pericarpium Citri Reticulatae with stable isotope-labeled internal standards. Validation demonstrated robust linearity (R2 >= 0.9990) across a 0.2-20 ng/mL calibration range for all analytes, with limits of detection (LODs) and quantification (LOQs) of 0.05 mu g/kg and 0.2 mu g/kg, respectively. The average recoveries at three spiked concentrations ranged from 96.4 to 113.0%, with relative standard deviations (RSDs) of 3.0-8.9%. The scientific value of this study lies in providing the first quantitative data on ZEN contamination (detected at 0.272-0.429 mu g/kg) in commercial Pericarpium Citri Reticulatae. The developed protocol exhibits exceptional sensitivity, reproducibility, and reliability, establishing a critical analytical benchmark for the quality control and risk assessment of this traditional dual-use food and medicine product.
Belamcanda chinensis (BC) is a traditional Chinese herbal medicine with a long history of use. However, there are few studies investigating the variations in chemical composition between unprocessed and processed BC. This study aimed to identify the differential compounds present after the processing of BC and to establish a scientific basis for optimizing its processing technology and quality control. In this study, three types of processed BC products were prepared based on relevant literature and historical texts: water extract of rice-processed (RB), leaves of Phyllostachys bambusoides Sieb. et Zucc-processed (PB), and a combination of water extract of rice with leaves of Phyllostachys bambusoides Sieb. et Zucc-processed (RPB). Ultra performance liquid chromatography (UPLC) fingerprint analysis was performed on an Agilent 1290 liquid chromatograph to evaluate the similarity of the 10 principal flavonoids among different BC samples. Additionally, an untargeted metabolomics approach using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was utilized to identify differential metabolites. Fingerprint analysis showed no significant differences in the 10 main flavonoids between unprocessed and processed samples. Untargeted metabolomics identified 85 differential metabolites, with 57, 60, and 63 metabolites detected in the RB, PB, and RPB processed groups, respectively. Compared with raw BC, the RB group showed increased levels of 16 metabolites and decreased levels of 41; the PB group exhibited 11 upregulated and 49 downregulated metabolites; while the RPB group demonstrated 15 elevated and 48 reduced metabolites. Among these processed groups, PB and RPB exhibited more similar metabolic profiles compared to RB. These findings represent the first systematic investigation into the chemical composition of processed BC, thereby addressing a critical gap in the existing research. Furthermore, they establish a scientific foundation for optimizing processing techniques and enhancing quality control, while also contributing to the modernization and reinterpretation of traditional processing theories.
BACKGROUND:Turmeric (Curcuma longa L.) is widely used as both a food and medicinal herb, exhibiting potent hypolipidemic properties. Although traditional turmeric decoctions are typically prepared with water or low-concentration alcohol, how alcohol affects the composition and bioactivity of turmeric decoction-derived exosome-like nanoparticles (TELNs) remains largely unknown. OBJECTIVES:This study elucidates the impact of low-concentration alcohol on the physicochemical characterization and metabolites of TELNs and confirms their potential in treating metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS:This study isolated TELNs from decoctions prepared with different alcohol concentrations (0%, 10%, and 20%, respectively) using a size exclusion chromatograph. Their morphology, particle size, concentration, and zeta potential were characterized and compared. Untargeted metabolomics was further employed to analyze differences in TELNs exposed to different alcohol concentrations. A mouse model of MASLD was established through high-fat diet induction. Subsequently, the therapeutic efficacy of TELNs extracted with different alcohol concentrations was evaluated through oral administration. RESULTS:The results indicated that although alcohol concentration did not affect the physicochemical properties of TELNs, it significantly altered their metabolite composition. Animal experiments of MASLD showed that oral administration of TELNs in all groups could ameliorate MASLD [serum total cholesterol, low-density lipoprotein cholesterol, atherogenic index, triglycerides (TG), aspartate aminotransferase, alanine aminotransferase, liver TG, interleukin-6, and tumor necrosis factor-α, all P < 0.05] with the 0% alcohol group exhibiting the most pronounced therapeutic effect (serum low-density lipoprotein cholesterol, atherogenic index, TG, liver TG, all P < 0.05). CONCLUSIONS:This study elucidates the impact of low-concentration alcohol on the physicochemical characterization and metabolites of TELNs and confirms their potential in treating MASLD. By integrating traditional turmeric decoction preparation methods with modern nanotechnology, this research provides new insights into the application of turmeric and the effects of alcohol on TELNs.
Translational pharmacological research on traditional medicines lays the foundation for precisely understanding how the medicines function in the body to deliver therapeutic benefits. Borneolum syntheticum (Bingpian) is commonly used in Chinese herbal medicines for coronary heart disease, but its specific cardiovascular impact remains poorly understood. Isoborneol, a constituent of Bingpian, has been found to reduce lipid accumulation in macrophages in vitro, but its oral bioavailability is limited. This investigation aimed to evaluate anti-atherosclerotic effects of Bingpian, based on understanding its first-pass metabolism. Human subjects orally received an herbal medicine containing Bingpian and their plasma samples were analyzed to identify the major circulating compounds of Bingpian, with the metabolism that was also characterized in vitro and in mice. The identified compounds were evaluated for their ability to inhibit macrophage foam-cell formation induced by oxidized low-density lipoprotein. Furthermore, the anti-atherosclerotic effect of repeatedly dosed Bingpian was assessed in ApoE-/- mice fed a high-fat diet. In human subjects, the major circulating compounds of Bingpian were metabolites, rather than their precursor constituents borneol and isoborneol. These constituents were efficiently absorbed in the intestinal tract but underwent significant first-pass metabolism, involving UGT2B7-mediated glucuronidation into borneol-2-O-glucuronide and isoborneol-2-O-glucuronide, respectively, and CYP2A6/2B6/3A-mediated oxidation both into camphor. Despite their poor membrane permeability, hepatic efflux of borneol-2-O-glucuronide and isoborneol-2-O-glucuronide into the systemic circulation was enhanced by MRP3/4. The circulating metabolites, particularly their combinations, markedly inhibited macrophage foam-cell formation induced by oxidized low-density lipoprotein in vitro. Sub-chronic administration of Bingpian (30 mg·kg-1·d-1, i.g.) for 12 weeks significantly decreased atherosclerotic lesion size and enhanced plaque stability in ApoE-/- mice. Systemic exposure to Bingpian metabolites in mice closely resembles that in humans, suggesting that the pharmacodynamic effects of Bingpian in mice are likely applicable to humans. Overall, the cardiovascular benefits of Bingpian involve reducing atherosclerosis by inhibiting foam-cell formation through its metabolites. This investigation supports that oral Bingpian could be a druggable agent for reducing atherosclerosis.
Rice allelopathy is a natural method of weed control that is regarded as an eco-friendly practice in agroecology. The root growth of allelopathic rice at the seedling stage plays an important role in its weed control. Our study characterizes a plant hormone that promotes root growth, abscisic acid (ABA), to explore its role in the induction of rice allelopathy. Increasing the root morphology traits (root length, root tip number, and root biomass) in rice using different concentrations of exogenous ABA resulted in increased inhibitory ratios against barnyard grass (Echinochloa crus-galli), both in a hydroponic experiment and pot test. In particular, the relative proportion of induced allelopathy to total allelopathy in non-allelopathic rice Lemont (Le) was higher than that in allelopathic rice PI31277 (PI). The total content of phenolic acid, which is an important allelochemical in rice, as previously reported, was significantly elevated in the root exudates of both PI and LE. The gene expression levels of OsPAL, OsC4H, and OsCOL related to phenolic acid synthesis were also up-regulated, with a higher regulatory fold in PI. ABA also increased the expression of OsKSL4 and CYP75B4 involved in the biosynthesis of momilactone B and tricin. Moreover, low concentrations of exogenous ABA mainly positively regulate the expression of OsIAA11, an AUX/IAA transcription factor gene, in the root of PI and Le. These findings suggest that the application of ABA could significantly enhance the weed-suppressive activity of both rice cultivars through regulating root growth and the synthesis of allelochemicals secreted by rice roots, providing an option for the improvement of rice allelopathy through chemical induction.
ObjectiveTo observe the effect of combined acupuncture and medication on hyperarousal state and serum copeptin (CPT) in patients with chronic insomnia (CI), and to explore its possible mechanism of action.MethodsA total of 70 CI patients meeting the inclusion criteria were divided into an observation group and a control group by the random number table method, with 35 cases in each group. The control group was given estazolam tablets before bedtime, 1 mg/time, once a day. The observation group was treated with additional Yi Nao An Shen acupuncture therapy (acupuncture for benefiting the brain and tranquillization) on the basis of the medication treatment, 4 times a week. After 4 weeks of treatment, the Pittsburgh sleep quality index (PSQI) score, insomnia severity index (ISI) score, pre-sleep arousal scale (PSAS) score, hyperarousal scale (HAS) score, and the change in serum CPT level were compared between the two groups.ResultsDuring the study, there were 2 dropout cases in the observation group and 1 dropout case in the control group. After treatment, the PSQI, ISI, PSAS, and HAS scores and the serum CPT level in both groups decreased compared with the same group before treatment, and the intra-group differences were statistically significant (P<0.05). After treatment, changes in each above scale score and the serum CPT level in the observation group were much more significant and were statistically different from those in the control group (P<0.05).ConclusionAcupuncture plus medication can improve sleep quality, reduce the degree of insomnia, and regulate hyperarousal state in patients with CI, and its mechanism of action may be related to the down-regulation of serum CPT level.
疼痛是人类最常见的症状之一,而导致疼痛产生最主要的一类问题当属筋骨病.随着现代人生活习惯、环境的改变,筋骨疾患人群日益增多,其所带来的疼痛、功能障碍等症状严重影响人们正常生活和工作.常见的筋伤骨病多属中医"筋痹""骨痹"范畴,文章试从筋与骨的关系、筋痹与骨痹的临床症状、病因病机及转归预后等方面理清二者关系,旨在对提升中医诊疗筋骨病的精确性有所裨益,进而减轻患者痛苦、提高生活质量.
ImportancePrevious research has suggested that Xuebijing injection (XBJ), an herbal-based intravenous preparation, may reduce mortality among patients with sepsis.ObjectiveTo determine the effect of XBJ vs placebo on 28-day mortality among patients with sepsis.Design, Setting, and ParticipantsThe Efficacy of Xuebijing Injection in Patients With Sepsis (EXIT-SEP) trial was a multicenter, randomized double-blind, placebo-controlled trial conducted in intensive care units at 45 sites and included 1817 randomized patients with sepsis (sepsis 3.0) present for less than 48 hours. Patients aged 18 to 75 years with a Sequential Organ Failure Assessment score of 2 to 13 were enrolled. The study was conducted from October 2017 to June 2019. The final date of follow-up was July 26, 2019. Data analysis was performed from January 2020 to August 2022.InterventionsThe patients were randomized to receive either intravenous infusion of XBJ (100 mL, n = 911) or volume-matched saline placebo (n = 906) every 12 hours for 5 days.Main Outcomes and MeasuresThe primary outcome was 28-day mortality.ResultsAmong the 1817 patients who were randomized (mean [SD] age, 56.5 [13.5] years; 1199 [66.0%] men), 1760 (96.9%) completed the trial. In these patients, the 28-day mortality rate was significantly different between the placebo group and the XBJ group (230 of 882 patients [26.1%] vs 165 of 878 patients [18.8%], respectively; P < .001). The absolute risk difference was 7.3 (95% CI, 3.4-11.2) percentage points. The incidence of adverse events was 222 of 878 patients (25.3%) in the placebo group and 200 of 872 patients (22.9%) in the XBJ group.Conclusions and RelevanceIn this randomized clinical trial among patients with sepsis, the administration of XBJ reduced 28-day mortality compared with placebo.Trial RegistrationClinicalTrials.gov Identifier: NCT03238742
Importance Previous research has suggested that Xuebijing injection (XBJ), an herbal-based intravenous preparation, may reduce mortality among patients with sepsis.Objective To determine the effect of XBJ vs placebo on 28-day mortality among patients with sepsis.Design, Setting, and Participants The Efficacy of Xuebijing Injection in Patients With Sepsis (EXIT-SEP) trial was a multicenter, randomized double-blind, placebo-controlled trial conducted in intensive care units at 45 sites and included 1817 randomized patients with sepsis (sepsis 3.0) present for less than 48 hours. Patients aged 18 to 75 years with a Sequential Organ Failure Assessment score of 2 to 13 were enrolled. The study was conducted from October 2017 to June 2019. The final date of follow-up was July 26, 2019. Data analysis was performed from January 2020 to August 2022.Interventions The patients were randomized to receive either intravenous infusion of XBJ (100 mL, n = 911) or volume-matched saline placebo (n = 906) every 12 hours for 5 days.Main Outcomes and Measures The primary outcome was 28-day mortality.Results Among the 1817 patients who were randomized (mean [SD] age, 56.5 [13.5] years; 1199 [66.0%] men), 1760 (96.9%) completed the trial. In these patients, the 28-day mortality rate was significantly different between the placebo group and the XBJ group (230 of 882 patients [26.1%] vs 165 of 878 patients [18.8%], respectively; P < .001). The absolute risk difference was 7.3 (95% CI, 3.4-11.2) percentage points. The incidence of adverse events was 222 of 878 patients (25.3%) in the placebo group and 200 of 872 patients (22.9%) in the XBJ group.Conclusions and Relevance In this randomized clinical trial among patients with sepsis, the administration of XBJ reduced 28-day mortality compared with placebo.
Background & Aims: The effect fraction of Bletilla striata (Thunb.) Reichb.f. (EFBS), a phenolic -rich extract, has significant protective effects on lipopolysaccharide (LPS)-induced acute lung injury (ALI), but its composition and molecular mechanisms are unclear. This study elucidated its chemical composition and possible protective mechanisms against LPS-induced ALI from an antioxidant perspective. Methods: EFBS was prepared by ethanol extraction, enriched by polyamide column chromatography, and characterized using ultra -performance liquid chromatography/time-of-flight mass spectrometry. The LPS-induced ALI model and the RAW264.7 model were used to evaluate the regulatory effects of EFBS on oxidative stress, and transcriptome analysis was performed to explore its possible molecular mechanism. Then, the pathway by which EFBS regulates oxidative stress was validated through inhibitor intervention, flow cytometry, quantitative PCR, western blotting, and immunofluorescence techniques. Results: A total of 22 compounds in EFBS were identified. The transcriptome analyses of RAW264.7 cells indicated that EFBS might reduce reactive oxygen species (ROS) production by inhibiting the p47phox/NADPH oxidase 2 (NOX2) pathway and upregulating the nuclear factor erythroid 2 -related factor 2 (Nrf2)/heme oxygenase1 (HO -1) pathway. Both in vitro and in vivo data confirmed that EFBS significantly inhibited the expression and phosphorylation of p47phox protein, thereby weakening the p47phox/NOX2 pathway and reducing ROS production. EFBS significantly increased the expression of Nrf2 in primary peritoneal macrophages and lung tissue and promoted its nuclear translocation, dose -dependent increase in HO -1 levels, and enhancement of antioxidant activity. In vitro, both Nrf2 and HO -1 inhibitors significantly reduced the scavenging effects of EFBS on ROS, further confirming that EFBS exerts antioxidant effects at least partially by upregulating the Nrf2/HO-1 pathway. Conclusions: EFBS contains abundant phenanthrenes and dibenzyl polyphenols, which can reduce ROS production by inhibiting the p47phox/NOX2 pathway and enhance ROS clearance activity by upregulating the Nrf2/HO1 pathway, thereby exerting regulatory effects on oxidative stress and improving LPS-induced ALI.
目的:通过回顾分析古代医家针灸防治疫病的经验,结合针灸治疗相关呼吸道系统传染病的循证证据,挖掘针灸防治急性传染病的腧穴处方和诊疗思路,为针灸防治新型冠状病毒肺炎(Corona Virus Disease 2019,COVID-19)(简称新冠肺炎)提供间接临床证据.方法:检索古代中医针灸经典、现代研究证据和新型冠状病毒肺炎诊疗方案.提取并分析以下数据:证据来源、发表或发布的时间、作者、治疗手段、目标疾病、效果和不良反应.数据分析以定性描述的方法为主.采用Microsoft Excel 2010软件建立数据库并进行频数统计.结果:中医早在内经时代就系统地阐述了疫病的发生机制、治疗方法及预防措施,并将针灸疗法作为治疗疫病的主要方法.2项临床试验表明针灸治疗病毒性肺炎有效,2项实验证明针灸可抑制或调节相关炎性因子水平.结合《针灸干预新型冠状病毒肺炎指导意见》《新型冠状病毒肺炎恢复期中医康复指导建议(试行)》和《新型冠状病毒感染的肺炎诊疗方案(第6版)》辨证分型,提出了针灸干预新冠肺炎的诊疗思路.结论:针灸防治新冠肺炎切实可行性且具有巨大发展潜力,但是仍需大样本的临床试验证明其有效性、安全性.
Xiaoqinglong decoction (XQLD), a classic prescription of Traditional Chinese Medicine, has already been used clinically to cure acute lung injury (ALI), but its mechanism remains unclear. This subject aimed to explore the preventive role of XQLD in septic ALI rats besides its effects on angiotensin-converting enzyme (ACE)2 and its downstream factors. After, respectively, administrated with different concentrations of XQLD (6.25 g/kg/d, 12.5 g/kg/d, 25 g/kg/d) for 5 days and dexamethasone (DEX, 1 mg/kg) for 0.5 h, the rat models of ALI were established by intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg) for 24 h. All rats were evaluated by lung function test, arterial blood gas analysis, morphological observation, lung wet/dry (W/ D ) ratio, and the lung injury score. The levels of malonaldehyde (MDA), superoxide dismutase (SOD), interleukin (IL)-1 β , tumor necrosis factor (TNF)- α , and angiotensin (Ang) (1–7) in the lung were measured through biochemical and ELISA kits. The expressions of angiotensin-converting enzyme (ACE)2, mitochondrial assembly receptor (MasR), and nuclear factor (NF)- κ B in lung tissue were detected by qRT-PCR and western blotting. Positive reaction cells of MasR were observed by immunohistochemistry. The results show that XQLD significantly ameliorated septic lung injury including edema and hemorrhage, as well as improved pulmonary function and arterial blood gas. Furthermore, XQLD markedly decreased the levels of IL-1 β , TNF- α , MDA, and NF- κ B while increased the levels of SOD, Ang (1–7), ACE2, and MasR in septic ALI rats. Pearson correlation showed that the expressions of ACE2 were inversely related to IL-1 β , TNF- α , MDA, and NF- κ B and positively correlated with SOD contents. Our data indicated that XQLD pretreatment alleviated inflammation and oxidative damage in septic ALI rats, which might be related to the up-regulation of ACE2-Ang (1–7)-MasR axis and inhibition of the NF- κ B pathway.
To observe the effects of electroacupuncture (EA) pretreatment on M1 polarization of alveolar macrophages (AMs) in rats with acute lung injury (ALI) induced by lipopolysaccharide (LPS), and to explore the potential protective mechanism of EA. Forty Sprague-Dawley rats were randomly divided into a normal group, a model group, and three groups of EA pretreatment [including a Chize (LU5) group, a Zusanli (ST36) group and a Chize (LU5) plus Zusanli (ST36) group], with eight rats in each group. The model rats of ALI were established by instilling LPS [2 mg/(kg-bw)] into the trachea of rats for 3 h. The rats in each EA pretreatment group were pretreated with EA for 30 min per day at the corresponding bilateral acupoints 6 d before instilling LPS. Three hours after modeling, the pulmonary function of the rats was tested, and the lung tissue was taken to calculate the ratio of lung wet weight to dry weight (W/D). The pathological lung changes and the injury score were observed by hematoxylin-eosin staining. The contents of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and myeloperoxidase (MPO) in rat’s bronchoalveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent assay. The mRNA and protein expression levels of Ml macrophage markers clusters of differentiation 86 (CD86), inducible nitric oxide synthase (iNOS), and its signaling pathway factor Toll-like receptor (TLR) 4, and nuclear factor-KB (NF-kB) p65 in the alveoli were detected by fluorescence quantitative polymerase chain reaction and Western blot, respectively. After being induced by LPS, the pulmonary function of the model rats showed that the forced expiratory volume in 0.1 s (FEV0.1), forced expiratory volume in 0.3 s (FEV0.3), and their respective ratios of FEV to forced vital capacity (FVC) (including FEV0.1/FVC and FEV0.3/FVC) were significantly decreased (P<0.01), while the W/D of lung tissue was increased (P<0.01). The score of lung injury was significantly higher (P<0.01). The contents of TNF-α, IL-1β, and MPO in the BALF and the mRNA and protein expression levels of CD86, iNOS, TLR4, and NF-kB p65 in the lung tissue were significantly increased (P<0.01). After EA pretreatment, the FEV0.1, FEV0.3, FEV0.1/FVC, and FEV0.3/FVC were significantly increased, the lung injury score decreased significantly, and the contents of TNF-α, IL-1β, and MPO in the BALF and the expression levels of CD86, iNOS, TLR4, and NF-kB p65 mRNAs and proteins in the alveoli decreased significantly (P<0.05 or P<0.01). Compared with the other two single acupoint groups, the contents of TNF-α, IL-1Pβ, and MPO in the BALF and the expression levels of CD86, iNOS, TLR4, and NF-kB p65 mRNAs in the alveoli in the Chize (LU5) plus Zusanli (ST36) group were significantly lower (P<0.01). EA pretreatment at Chize (LU5) and Zusanli (ST36) can inhibit inflammation and reduce pulmonary injury in ALI rats induced by LPS. The effect of the combination of Chize (LU5) and Zusanli (ST36) is better than that of using these two acupoints separately, and its mechanism may be related to the inhibition of AMs’ M1 polarization by down-regulation TLR4/NF-KB signaling pathway.