Stroke is the second-leading global cause of death. The damage attributed to the immune storm triggered by ischemia–reperfusion injury (IRI) post-stroke is substantial. However, data on the transcriptomic dynamics of pyroptosis in IRI are limited. This study aimed to analyze the expression of key pyroptosis genes in stroke and their correlation with immune infiltration. Pyroptosis-related genes were identified from the obtained middle cerebral artery occlusion (MCAO) datasets. Differential expression and functional analyses of pyroptosis-related genes were performed, and differences in functional enrichment between high-risk and low-risk groups were determined. An MCAO diagnostic model was constructed and validated using selected pyroptosis-related genes with differential expression. High- and low-risk MCAO groups were constructed for expression and immune cell correlation analysis with pyroptosis-related hub genes. A regulatory network between pyroptosis-related hub genes and miRNA was also constructed, and protein domains were predicted. The expression of key pyroptosis genes was validated using an MCAO rat model. Twenty-five pyroptosis genes showed differential expression, including four hub genes, namely WISP2, MELK, SDF2L1, and AURKB. Characteristic genes were verified using real-time quantitative PCR analyses. The high- and low-risk groups showed significant expression differences for WISP2, MELK, and SDF2L1. In immune infiltration analysis, 12 immune cells showed differences in expression in MCAO samples. Further analysis demonstrated significant positive correlations between the pyroptosis-related hub gene SDF2L1 and immune cell-activated dendritic cells in the high-risk group and immune cell natural killer cells in the low-risk group. This study identified four pyroptosis-related hub genes, with elevated WISP2, MELK, and SDF2L1 expression closely associated with the high-risk group. The analysis of inflammatory cell types in immune infiltration can predict ischemic stroke risk levels and help to facilitate treatment.

Cycloastragenol, a triterpenoid saponin extracted from Astragalus membranaceus, exerts several pharmacological effects. However, its mechanism of action in acute lung injury treatment remains unclear. This study was conducted to test the hypothesis that cycloastragenol can inhibit lipopolysaccharide (LPS)-induced acute lung injury and investigate the underlying molecular mechanisms. This study systematically explored the effects and mechanism of action of cycloastragenol in LPS-induced acute lung injury treatment using network pharmacology, molecular docking, molecular dynamics simulation, and experimental validation. Gene Ontology and Kyoto Encyclopedia of Gene and Genomes enrichment analyses indicated that the effects of cycloastragenol are mediated by inflammation- and apoptosis-related genes. Both in vitro and in vivo experiments were conducted to assess the effectiveness of cycloastragenol in acute lung injury treatment. Lung function was evaluated using a pulmonary function test system with indicators, such as peak expiratory flow, minute ventilation, and lung resistance. The expression of inflammatory factors and apoptosis-related proteins was evaluated using Western blot analysis, quantitative real-time polymerase chain reaction, and immunofluorescence. Apoptosis in lung tissue and mouse primary peritoneal macrophages was assessed using terminal deoxynucleotidyl transferase dUTP nick-end labelling staining and flow cytometry, respectively. Cycloastragenol effectively alleviated pulmonary dysfunction and edema, mitigated histopathological damage, and suppressed the activation of both the NF-κB p65 and Akt signaling pathways induced by LPS, ultimately leading to reduced inflammation and apoptosis. The results suggest that cycloastragenol alleviates acute lung injury by exerting anti-inflammatory and anti-apoptotic effects. These findings suggest that cycloastragenol could be a potential therapeutic candidate for preventing and treating ALI.

Abstract Background: Stroke is the second-leading global cause of death. The immune storm triggered by ischemia-reperfusion injury after stroke is a crucial damaging factor. This study analyzed the expression of key pyroptosis genes in stroke and their correlation with immune infiltration. Methods: Middle Cerebral Artery Occlusion datasets were obtained and pyroptosis-related genes were identified. Differential expression and functional analyses of pyroptosis-related genes were performed. Differences in functional enrichment between high-risk and low-risk groups were determined. After selecting pyroptosis-related genes with differential expression, a MCAO diagnostic model was constructed and validated. High and low-risk MCAO groups were constructed for expression and immune cell correlation analysis with pyroptosis-related hub genes. A regulatory network between pyroptosis-related hub genes and miRNA was built, and protein domains were predicted. The expression of key pyroptosis genes was validated in the MCAO rat model. Results: Twenty-five pyroptosis genes showed differential expression, including four hub genes (WISP2, MELK, SDF2L1, and AURKB). The high- and low-risk groups showed significant expression differences for WISP2, MELK and SDF2L1. In immune infiltration analysis, 12 immune cells exhibited expression differences in MCAO samples. Further analysis demonstrated significant positive correlations between the pyroptosis-related hub gene SDF2L1 and immune cell-activated dendritic cells in the high-risk group and immune cell natural killer cells in the low-risk group. Conclusion: This study identified four pyroptosis-related hub genes, with elevated WISP2, MELK, and SDF2L1 expression closely associated with the high-risk group. Analysis of inflammatory cell types in immune infiltration provides a theoretical basis for predicting ischemic stroke risk levels and treatment.

Brain injury remains a major problem in patients suffering cardiac arrest (CA). Disruption of the blood-brain barrier (BBB) is an important factor leading to brain injury. Therapeutic hypothermia is widely accepted to limit neurological impairment. However, the efficacy is incomplete. Hydrogen sulfide (H2S), a signaling gas molecule, has protective effects after cerebral ischemia reperfusion injury. This study showed that combination of hypothermia and H2S after resuscitation was more beneficial for attenuated BBB disruption and brain edema than that of hypothermia or H2S treatment alone. CA was induced by ventricular fibrillation for 4 min. Hypothermia was performed by applying alcohol and ice bags to the body surface under anesthesia. We used sodium hydrosulphide (NaHS) as the H2S donor. We found that global brain ischemia induced by CA and cardiopulmonary resuscitation (CPR) resulted in brain edema and BBB disruption; Hypothermia or H2S treatment diminished brain edema, decreased the permeability and preserved the structure of BBB during the early period of CA and resuscitation, and more importantly, improved the neurologic function, increased the 7-day survival rate after resuscitation; the combination of hypothermia and H2S treatment was more beneficial than that of hypothermia or H2S treatment alone. The beneficial effects were associated with the inhibition of matrix metalloproteinase-9 expression, attenuated the degradation of the tight junction protein occludin, and subsequently protected the structure of BBB. These findings suggest that combined use of therapeutic hypothermia and hydrogen sulfide treatment during resuscitation of CA patients could be a potential strategy to improve clinical outcomes and survival rate.

Liver hepatocellular carcinoma (LIHC) remains a lethal disease for humans. Immune checkpoint inhibitors (ICIs) targeting PD1/PD-L1 and CTLA4 offered new hopes for advanced-stage patients. Novel immune biomarkers and therapeutic targets are urgently needed. For the first time, we evaluated the expression and prognostic value of Layilin (LAYN) using in silico analyses and uncovered the carcinogenic role of LAYN in LIHC. The HCG18/hsa-mir-148a/LAYN axis was predicted as the upstream mechanism. Moreover, gene set enrichment analysis (GSEA) revealed that LAYN and its coexpressed genes primarily participated in immune response pathways, and LAYN expression was found significantly correlated with tumor immune cell infiltration in LIHC tissues. In general, our data provided evidence that HCG18/hsa-mir-148a-regulated high expression of LAYN is associated with immune cell infiltration and unfavorable prognosis of LIHC patients.

Corneal abrasion during radical thyroidectomy is a rare complication and is infrequently addressed in the literature. Here, we present the case of a young female patient who underwent radical thyroidectomy with general anesthesia. During the operation, the eyes were being naturally closed without protection measures, and corneal abrasion of the left eye occurred after the operation. The lesion had completely resolved with no sequelae after treatment. Therefore, preventive measures and attentive care may help reduce the incidence of corneal abrasion in patients undergoing radical thyroidectomy.

Ferroptosis is a new type of cell death that was discovered in recent years and usually accompanied by a large amount of iron accumulation and lipid peroxidation during the cell death process. Ferroptosis plays a key role in brain injury. Ferroptosis inhibitors can effectively improve iron homeostasis, lipid metabolism, redox stabilization, neuronal remodeling, and functional recovery after trauma. In this review, we summarized the latest molecular mechanisms of ferroptosis and current research on ferroptosis, especially its role in the progression of cerebral ischemia, cerebral hemorrhage, traumatic brain injury and other acute brain injury. These findings will provide evidence for further understanding the pathogenesis of brain injury and searching new targets for the treatment of brain injury.

目的 探讨腹腔镜手术体位对脑血管阻力及血流量的影响.方法 选取2020年1～7月在皖南医学院第一附属医院择期行腹腔镜手术的女性患者60例,按随机数字表法,分为试验组(T组)与对照组(R组),每组30例.试验组按术中体位需要调整为头低位(-30°),对照组为头高位并向左侧倾斜(30°).采用无创多普勒超声测量,比较T1(置入喉罩后5分钟)、T2(气腹体位变化后即刻)、T3(气腹体位变化30分钟)、T4(关气腹体位恢复后10分钟)4个时间点双侧颈内动脉和椎动脉血管阻力指数(RI)的差异,并对两组患者脑动脉血流量(CBFV)进行分析.观察比较两组患者T1～ T44个时点心率(HR)、平均动脉压(MAP)和呼气末二氧化碳分压(PETCO2)的差异.结果 两组患者双侧颈内动脉和椎动脉RI组间比较,差异有统计学意义(P＜0.05),存在时间、交互效应.在T2～ T4时,T组双侧椎动脉和颈内动脉RI高于R组(P＜0.05);与T1比较,在T2～T3时点,T组右椎动脉和左颈内动脉RI增高(P＜0.05).两组患者CBFV组间比较,差异无统计学意义(P＞0.05);在T2时,T组CBFV高于R组(P＜0.05);与T1比较,在T2和T3时点,T组CBFV增加(P＜0.05).两组患者HR、MAP、PETC02组间比较,差异无统计学意义(P＞0.05).在T3时点,T组MAP高于R组(P＜0.05);与T1比较,在T2～T4时点,T组MAP增加(P＜0.05).结论 腹腔镜手术中头低位可引起椎动脉和颈内动脉血管阻力指数及血流量增加.

Objective To evaluate the changes in expression of cold-inducible RNA-binding protein (CIRP) in hippocampus during brain injury in a rat model of cardiac arrest-cardiopulmonary resuscitation.Methods Seventv-two clean-grade healthy male Sprague-Dawley rats,weighing 280-350 g,aged 8-10 weeks,were divided into 2 groups using a random number table:sham operation group (S group,n=18) and ischemia-reperfusion group (I/R group,n=54).Tracheal intubation was performed and artery and veins were punctured in group S.Ventricular fibrillation was induced by transoesophageal cardiac pacing to establish the model of cardiac arrest in group I/R.Rats were sacrificed at 12,24 and 48 h after resuscitation and the hippocampus was harvested for determination of CIRP,tumor necrosis factor-alpha (TNF-α) and interleukin-lbeta (IL-1β) protein and mRNA expression (by quantitative polymerase chain reaction or Western blot) and for determination of pathological changes of hippocampi (with a light microscope).Results Compared with group S,the expression of CIRP mRNA in hippocampus was up-regulated at 24 and 48 h after resuscitation,the expression of TNF-α mRNA was up-regulated at 12,24 and 48 h after resuscitation,the expression of IL-1β mRNA was up-regulated at 12 and 24 h after resuscitation,and the expression of CIRP,TNF-α and IL-1β was up-regulated at 12,24 and 48 h after resuscitation in group I/R (P＜0.05).Pathological changes in hippocampal CA1 region were found in group I/R.Conclusion The expression of CIRP in hippocampus is up-regulated,which promotes central inflammatory responses during brain injury in a rat model of cardiac arrest-cardiopulmonary resuscitation.

目的 探讨心跳骤停心肺复苏后大鼠海马冷诱导RNA结合蛋白(CIRP)的表达变化,探讨其在心跳骤停心肺复苏后脑损伤中的作用机制.方法 健康成年雄性SD大鼠36只,采用随机数字表法均分成2组(n=18):Sham组和缺血再灌注48 h组(I/R 48 h组).Sham组只给予气管插管和动静脉穿刺,不给予电刺激;I/R 48h组大鼠气管插管和动静脉穿刺后,经食管电刺激诱发心室纤颤建立心跳骤停模型.复苏后48 h,行神经功能评分;苏木精-伊红染色观察海马CA1区锥体细胞形态改变;免疫组化法检测海马中小胶质细胞的活化;Western blot检测海马组织CIRP总蛋白和浆蛋白表达.结果 与Sham组相比,I/R48h组的神经功能评分明显降低(P＜0.05);海马CA1区神经元死亡数目明显增多(P＜0.05);小胶质细胞激活面积在海马CA1区显著增加(P＜0.05);海马组织中CIRP总蛋白和浆蛋白表达明显增加(P＜0.05).结论 心跳骤停心肺复苏可诱导CIRP的高表达,CIRP可从细胞核移位到细胞质中,可能参与大鼠心跳骤停心肺复苏后脑组织损伤的早期炎症反应过程.

Objective: To investigate the effect of mild hypothermia combined with hydrogen sulfide on hippocampal endoplasmic reticulum stress (ERS) after global cerebral ischemia-reperfusion (I/R) injury. Methods: Sixty healthy male Sprague-Dawley rats, 8-10 week old, weighing 280-320 g, were randomly divided into 5 groups (n=12) using a random number table: sham operation group (group Sham), global cerebral I/R group (group I/R), hydrogen sulfide group (group H(2)S), mild hypothermia group (group MH) and hydrogen sulfide + mild hypothermia group (group H(2)S+ MH). Cardiac arrest was induced with transoesophageal cardiac pacing followed by cardiopulmonary resuscitation to establish the global cerebral I/R model. The administration regimen for sodium hydrosulfide (NaHS) was as follows: Sodium hydrosulfide was intraperitoneal injection as a bolus of 2.5 mg/kg immediately restoration of spontaneous circulation. The implementation of mild hypothermia: wipe the body surface of rats with ethanol immediately after restoration of spontaneous circulation, and reduce the rectal temperature to 32-34 ℃ within 15 min, and maintain 6 h with the ice bag. At 72 h of reperfusion, neurological deficit was scored, and the rats were sacrificed (Neurological Deficit Scores, NDS), the expression of glucose-regulated protein 78 (GRP78), CHOP and Caspase-12 were detected by Western blot. After reperfusion 72 h, the hippocampal tissue were removed and stained with haematoxylin and eosin to examine the pathological findings in hippocampal CA1 area (under microscope). The apoptosis rate of hippocampal CA1 area cells was detected by TUNEL staining and the apoptosis index was calculated. Results: The expression levels of endoplasmic reticulum stress marker, GRP78, CHOP and Caspase-12, were upregulates during the global cerebral ischemia reperfusion injury, indicating activation of severe endoplasmic reticulum stress. The GRP78 contents of Sham group, I/R group, H(2)S group, MH group and H(2)S+ MH group were as follows: GRP78: 0.11±0.03, 1.11±0.10, 0.67±0.09, 0.66±0.08, 0.48±0.04, CHOP contents: 0.16±0.03, 1.60±0.11, 1.39±0.09, 1.34±0.08, 1.13±0.09, Caspase-12 contents: 0.09±0.02, 0.87±0.08, 0.65±0.08, 0.59±0.06, 0.45±0.06, the differences were statistically significant (F=147.569, 264.983, 119.356, all P<0.01). The apoptosis index of Sham group, I/R group, H(2)S group, MH group and H(2)S+ MH group were as follows: (1.83±0.75)%, (53.17±4.62)%, (35.17±2.14)%, (32.67±2.25)%, (17.83±2.79)%, the differences were statistically significant (F=284.962, P<0.01). The neurological deficit scores of Sham group, I/R group, H(2)S group, MH group and H(2)S+ MH group were as follows: 0%, (76±9)%, (54±5)%, (47±6)%, (35±6)%, the differences were statistically significant(F=135.218, P<0.01). Conclusion: Mild hypothermia combined with hydrogen sulfide alleviates hippocampal endoplasmic reticulum stress after global cerebral ischemia-reperfusion, and the combined effect is better than that of a single application.

Therapeutic hypothermia is effective to attenuate brain ischemia/reperfusion (I/R) injury after cardiac arrest, and multiple mechanisms have been proposed. Dynamin-related protein 1 (Drp1), a large GTPases of dynamin superfamily, predominantly controls mitochondrial fission and is related to IR-induced Cyt C release and apoptosis. However, the effect of therapeutic hypothermia on Drp1 and mitochondrial fission after cardiac arrest remains still unclear. In this study, non-cardiac arrest and post-cardiac arrest rats received 6-h normothermia (37-38°C) or therapeutic hypothermia (32-34°C), and the hippocampus was harvested at 6h and 72h after cardiac arrest. Results showed the expression of Drp1 and Cyt C increased after cardiac arrest, but therapeutic hypothermia partially reversed this increase at 6h after cardiac arrest. Transmission electron microscopy (TEM) also showed a change in morphology following therapeutic hypothermia after cardiac arrest. Moreover, therapeutic hypothermia could decrease the histopathological damage, inhibit the apoptosis of CA1 neurons and improve the survival and neurological outcomes at 72h after cardiac arrest. Taken together, our study demonstrates that therapeutic hypothermia is neuroprotective against global cerebral I/R injury, which is, at least partially, ascribed to the inhibition Drp1 and Cyt C expression and the protection of mitochondrial structure.

Objective To evaluate the effect of hydrogen sulfide on hippocampal endoplasmic reticulum stress during global cerebral ischemia-reperfusion (I/R) in rats.Methods Seventy-two pathogen-free healthy male Sprague-Dawley rats,weighing 280-320 g,aged 8-10 weeks,were divided into 3 groups (n=24 each) using a random number table:sham operation group (group Sham),global cerebral I/R group (group I/R) and global cerebral I/R plus sodium hydrosulfide group (group I/R+NaHS).Cardiac arrest was induced with transoesophageal cardiac pacing followed by cardiopulmonary resuscitation to establish the global cerebral I/R model.Immediately after recovery of spontaneous circulation,sodium hydrosulfide 2.5 mg/kg was intraperitoneally injected in group I/R+NaHS,and normal saline 5 ml/kg was given in group I/R.The hippocampi were immediately removed at 24 h of reperfusion for determination of the expression of glucose-regulated protein 78 (GRP78),C/EBP-homologous protein (CHOP) and caspase-12 in hippocampal tissues (by Western blot).At 1,3 and 7 days of reperfusion,the hippocampal tissues were obtained and stained with haematoxylin and eosin for examination of the pathological changes in hippocampal CA1 region (under a light microscope) and for determination of apoptosis in hippocampal cells (using TUNEL staining),and the apoptosis rate was calculated.Results Compared with group Sham,the apoptosis rate of hippocampal tissues at 1,3 and 7 days of reperfusion in group I/R and at 3 and 7 days of reperfusion in group I/R+NaHS were significantly increased,and the expression of GRP78,CHOP and caspase-12 in hippocampal tissues was significantly up-regulated in I/R and I/R+NaHS groups (P＜0.05).Compared with group I/R,the apoptosis rate of hippocampal tissues was significantly decreased,and the expression of GRP78,CHOP and caspase-12 was down-regulated at 1,3 and 7 days of reperfusion (P＜0.05),and the pathological changes were significantly attenuated in group I/R+NaHS.Conclusion The mechanism by which hydrogen sulfide reduces apoptosis in hippocampal cells is related to inhibition of endoplasmic reticulum stress during global cerebral I/R in rats.

Objective To investigate whether the nuclear factor E2 related factor/heme synthase-1 (Nrf2/HO-1) pathway is involved in the mechanism of hydrogen sulfide-induced reduction of blood brain barrier(BBB) injury in rats with cardiac arrest and the possible mechanism involved in the effect.Methods Cardiac arrest was induced with transoesophageal cardiac pacing followed by cardiopulmonary resuscitation to establish the cardiac arrest model and the time of ischemia was 4 min.140 adult male SD rats were randomly divided into five groups:sham operation group (Sham group,n=20),cardiac arrest model group (CPR group,n=30),sodium hydrogen sulfide (NaHS) group (n=30),NaHS+solvent group [NaHS+dimethyl sulfoxide (DMSO) group,n=30],NaHS+Nrf2 inhibitor retinoic acid(RA) group(NaHS+RA group,n=30).In Sham group,only anesthesia was performed,and the trachea was inserted through the mouth,and the catheters were performed via femoral artery and vein.The other four groups were all induced cardiac arrest by electrical stimulation.NaHS group and NaHS+RA group,rats received NaHS (0.5 mg/kg) at the start of CPR intravenously,followed by a continuous infusion of NaHS (1.5 mg ·kg-1 ·h-1) for 3 h.NaHS+RA group,RA was given i.p.daily at 10 mg/kg for 1 week before experiment and immediately after recovery.NaHS+DMSO group was given the same amount of solvent daily for 1 week before experiment and immediately after recovery.CPR group was given the same amount of normal saline at the start of CPR intravenously.After recovery,7 days were observed continuously and the survival condition was recorded,and neurological function were evaluated at 1,3 d,and 7 d after recovery,brain water content,BBB permeability and Nrf2,HO-1,BBB tight junction protein occludin expression was detected at 24 h after resuscitation,and the expression of matrix metalloproteinase-9(MMP-9) was detected by immunohistochemical staining.Results The survival rates,neurologic deficit scores (NDS),Nrf2 and HO-1 expression,and occludin expression in NaHS group were higher than CPR group (P＜0.05),while the NaHS+RA group was lower than the NaHS group(P＜0.05).The brain water content and evans blue(EB) content,and MMP-9 positive cells number in NaHS group were significantly lower than that in CPR group(P＜0.05),and the content of brain water content and EB content,and MMP-9 positive cells number in NaHS+RA group were higher than that in NaHS group (P＜0.05).There was no significant difference between the NaHS group and the NaHS+DMSO group (P＞0.05).Conclusions Hydrogen sulfide could reduce the BBB damage in rats with cardiac arrest,which may be related to the activation of Nrf2/HO-1 pathway,inhibiting the expression of MMP-9 and decreasing the loss of occludin protein.

Background: Hydrogen-rich saline can selectively scavenge reactive oxygen species (ROS) and protect brain against ischemia reperfusion (I/R) injury. Endoplasmic reticulum stress (ERS) has been implicated in the pathological process of cerebral ischemia. However, very little is known about the role of hydrogen rich saline in mediating pathophysiological reactions to ERS after I/R injury caused by cardiac arrest.Methods: The rats were randomly divided into three groups, sham group (n =30), ischemia/reperfusion group (n= 40) and hydrogen-rich saline group (n=40). The rats in experimental groups were subjected to 4 min of cardiac arrest and followed by resuscitation. Then they were randomized to receive 5 ml/kg of either hydrogen-rich saline or normal saline.Results: Hydrogen-rich saline significantly improves survival rate and neurological function. The beneficial effects of hydrogen-rich saline were associated with decreased levels of oxidative products, as well as the increased levels of antioxidant enzymes. Furthermore, the protective effects of hydrogen-rich saline were accompanied by the increased activity of glucose-regulated protein 78 (GRP78), the decreased activity of cysteinyl aspartate specific proteinase-12 (caspase-12) and C/EBP homologous protein (CHOP).Conclusions: Hydrogen-rich saline attenuates brain I/R injury may through inhibiting hippocampus ERS after cardiac arrest in rats. (C) 2017 Elsevier B.V. All rights reserved.

Objective To investigate the effect of mild hypothermia combined with mitochondrial divison inhibitor 1 in mitochondrial after cerebral ischemia-reperfusion (IR).Methods Fourty male healthy Sprague-Dawley (SD) rats, weighing 280-320 g, were randomly divided into 5 groups (n=8 each): group Sham, group IR, hypothermia group (group H), Mdivi-1 group (group M) and hypothermia+Mdivi-1 group (group HM).Animal models of global cerebral IR were established by transoesophageal cardiac pacing inducing cardiac arrest followed by cardiopulmonary resuscitation (ischemia 4 min and reperfusion 6 h).The group Sham was similarly treated to group IR except the cardiac arrest and cardiopulmonary resuscitation.In groups H and HM, the core temperature was cooled down to 32-34℃ within 15 min starting from the beginning of reperfusion, and maintained for 6 h.In the other groups, the core temperature was maintained at the normal temperature.In groups M and HM, the animals were given Mdivi-1 (1.2 mg/kg) intravenously at the beginning of the reperfusion and the other groups were given the same volumn of dimethylsnlfone (DMSO).After 6 h of reperfusion, the rats were sacrificed, and bilateral hippocampi were immediately removed for determination the protein level of dynamin-related proten 1 (Drp1) and cytochrome C (Cyt-C) expression by Western blot and obsevation of the mitochondrial structure of pyramidal cell in hippocampal CA1 under electronic microscope.Results Compared with group Sham, the expression of Drp1 and Cyt-C was up-regulated in groups IR, H, M and HM (P＜0.05).Compared with group IR, the expression of Drp1 and Cyt-C was down-regulated in groups H, M and HM (P＜0.05).Compared with groups H and M, the expression of Drp1 and Cyt-C was down-regulated in group HM (P＜0.05).There was no significant difference in the expression of Drp1 and Cyt-C between groups H and M.The mitochondria were rod-shaped with clear and sound structure in group Sham, while mitochondria showed various degree of fission, swollen structures, matrix deposit, vacuoles formation and cristae collapse in other groups.The changes of group HM were relatively slight.Conclusion Mild hypothermia combined with mitochondrial divison inhibitor 1 alleviate mitochondrial damage after global cerebral IR of rats.The combined effect is better than that of any individual application.

Objective To evaluate the efficacy of sodium hydrosulfide for improvement of cerebral protection provided by mild hypothermia in a rat model of cardiac arrest and resuscitation.Methods One hundred and forty pathogen-free healthy male Sprague-Dawley rats,weighing 280-320 g,aged 7-8 weeks,were randomly divided into 5 groups using a random number table:sham operation group (group S,n =20),cardiac arrest and resuscitation group (group CAR,n=30),sodium hydrosulfide group (group SH,n=30),mild hypothermia group (group MH,n=30) and sodium hydrosulfide plus mild hypothermia group (group SH+MH,n=30).Cardiac arrest was induced by transesophageal cardiac pacing,and cardiopulmonary resuscitation was started after 4 min untreated arrest.The administration regimen for sodium hydrosulfide was as follows:sodium hydrosulfide was intravenously injected as a bolus of 0.5 mg/kg immediately after restoration of spontaneous circulation followed by an infusion of 1.5 mg · kg-1,h-1 for 3 h.Mild hypothermia was performed as follows:the rectal temperature was cooled down to 32-34 ℃ by rubbing the body surface with ethanol within 15 min starting from the time point immediately after restoration of spontaneous circulation and maintained at this level for 4 h,and then increased to 38-39 ℃ within 2 h.The animals were observed for 7 consecutive days after resuscitation,the survival rate was recorded,and the neurological function was evaluated by the tape removal test.At 24 h after resuscitation,brain tissues were harvested for determination of brain water content,permeability of blood brain barrier,expression of occludin in hippocampi (by Western blot),and expression of matrix metalloproteinase-9 (MMP-9) in hippocampi (by immunohistochemical staining).Results Compared with group S,the survival rate was significantly decreased,the tape removal time was significantly prolonged,the brain water content and permeability of blood brain barrier were significantly increased,the expression of occludin was significantly downregulated,and the expression of MMP-9 was significantly up-regulated in CAR,SH,MH and SH+MH groups (P＜0.05).Compared with group CAR,the survival rate was significantly increased,the tape removal time was significantly shortened,the brain water content and permeability of blood brain barrier were significantly decreased,the expression of occludin was significantly up-regulated,and the expression of MMP-9 was significantly down-regulated in SH,MH and SH+MH groups,and the changes in the parameters mentioned above were more obvious in group SH+MH (P＜0.05).Conclusion Sodium hydrosulfide significantly improves cerebral protection provided by mild hypothermia in a rat model of cardiac arrest and resuscitation,and the mechanism is related to reduction of occludin degradation,down-regulation of MMP-9 expression and decrease in the permeability of blood brain barrier.

Objective To evaluate the effect of hypothermia on the expression of dynamin?related protein 1 ( Drp1) in brain tissues during global cerebral ischemia?reperfusion ( I∕R) in rats. Methods Thirty?six healthy male Sprague?Dawley rats, weighing 280-320 g, were divided into 3 groups ( n=12 each) using a random number table: sham operation group ( group Sham ) , global cerebral I∕R group ( group I∕R) and hypothermia group ( group H) . Cardiac arrest was induced by transoesophageal cardiac pacing followed by cardiopulmonary resuscitation to establish the global cerebral I∕R model in anesthetized rats in I∕R and H groups. In group H, the body temperature ( rectal temperature) was cooled down to 32-34 ℃ within 15 min starting from the beginning of reperfusion, and maintained at this level for 6 h. At 72 h of reperfusion, neurological deficit was scored, and the rats were sacrificed, and the whole brain was removed for examination of the pathological changes in hippocampal CA1 region and for determination of nor?mal pyramidal cell count and neuronal apoptosis in hippocampal CA1 region and expression of Drp1 and cy?tochrome c (Cyt c) in hippocampal tissues (by Western blot). The apoptosis rate was calculated. Re?sults Compared with group S, the neurological deficit score and apoptosis rate were significantly in?creased, and the number of normal pyramidal cells was decreased in I∕R and H groups, the expression of Drp1 and Cyt c in hippocampal tissues was significantly up?regulated in group I∕R ( P<0.05) , and no sig?nificant change was found in the expression of Drp1 and Cyt c in hippocampal tissues in group H ( P>0.05) . Compared with group I∕R, the neurological deficit score and apoptosis rate were significantly de?creased, the number of normal pyramidal cells was increased, and the expression of Drp1 and Cyt c in hip?pocampal tissues was down?regulated in group H ( P<0.05) . Conclusion The mechanism by which hypo?thermia inhibits cell apoptosis during global cerebral I∕R may be related to down?regulation of Drp1 expres?sion in rats.