SIRT1信号通路在白藜芦醇保护脑缺血再灌注损伤中的作用机制  

The Mechanism of SIRT1 Signaling Pathway in the Protective Effect of Resveratrol on Cerebral Ischemia - reperfusion Injury

作　　者：陈勇 周游[2] 金胜昔[2] 何婷[3] CHEN Yong;ZHOU You;JIN Shengxi;HE Ting(Shenzhen University General Hospital,Shenzhen 518055,Guangdong,China;Tianyou Hospital,Wuhan University of Science and Tech-nology,Wuhan 430065,Hubei,China;Tongren Hospital of WuHan University/Wuhan Third Hospital,Wuhan 430060,Hubei,China)

机构地区：[1]深圳大学总医院,深圳518055 [2]武汉科技大学附属天佑医院,武汉430065 [3]武汉大学附属同仁医院/武汉市第三医院,武汉430060

出　　处：《中西医结合心脑血管病杂志》2020年第1期59-64,共6页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：湖北省教育厅科学技术研究计划青年人才项目(No.Q20161109);湖北省自然科学基金青年基金(No.2015CFB645)

摘　　要：目的探讨白藜芦醇(Res)对大脑缺血再灌注损伤后大鼠神经元凋亡的影响及其作用机制。方法采用线栓法制作短暂性大脑中动脉栓塞(MCAO)模型。将60只SD大鼠随机分为假手术组(Sham组)、脑缺血再灌注模型组(MCAO组)、白藜芦醇低剂量(10 mg/kg)组(Res 10组)、白藜芦醇高剂量(30 mg/kg)组(Res 30组)。栓塞缺血2 h、再灌注24 h后对各组大鼠进行神经功能损伤评分、脑组织含水量及脑梗死体积评估,TUNEL染色检测细胞凋亡,同时测定缺血再灌注损伤缺血测脑组织中SIRT1、Bax、Caspase-3 mRNA表达水平。结果脑缺血再灌注后24 h,MCAO组脑梗死体积大于Sham组(P<0.01),神经功能损伤评分、脑组织含水量、TUNEL(+)细胞数及Bax mRNA、Caspase-3 mRNA表达量均明显高于Sham组(P<0.01),而SIRT1 mRNA表达量较Sham组明显降低(P<0.01)。与MCAO组比较,Res 10组、Res 30组脑梗死体积明显缩小(P<0.01),神经功能损伤评分、脑组织含水量、TUNEL(+)细胞数以及脑组织中Bax mRNA、Caspase-3 mRNA表达量明显降低(P<0.01),SIRT1 mRNA表达明显增加(P<0.01)。结论白藜芦醇可通过减轻缺血脑组织神经元凋亡对大鼠脑缺血再灌注损伤发挥神经保护作用,其可能通过激活SIRT1信号通路从而抑制或逆转脑缺血再灌注神经损伤的发生。Objective To observe the effect of resveratrol on neuronal apoptosis after cerebral ischemia-reperfusion injury,and to ex-plore its molecular mechanism.Methods The transient middle cerebral artery occlusion(MCAO)model was developed by suture method.Sixty SD rats were randomly divided into sham operation group,MCAO model group,low dose(10 mg/kg),and high dose(30 mg/kg)resveratral treatment group.After ischemia 2hours and 24 hours reperfusion,the neurological score,brain water content,and cerebral infarct volume were evaluated in each group.The neuronal apoptosis was observed by the TUNEL staining.The expression levels of SIRT1,Bax,and Caspase-3 in the ischemic cerebral tissue were measured.Results After 24 hours reperfusion,the cerebral infarct volume in MCAO group was significantly larger than that in Sham group(P<0.01),the neurological score,brain water content,TUNEL(+)cell number and the expression of Bax and Caspase-3 mRNA in the MCAO group were all significantly higher than those in the control group(P<0.01),while SIRT1 mRNA expression was significantly lower than that in Sham group.The cerebral infarct vol-ume in MCAO group was lower than those in low dose(10 mg/kg)and high dose(30 mg/kg)resveratral treatment groups(P<0.01).The neurological score,brain water content,TUNEL(+)cell number,and the Bax and Caspase-3 mRNA expression in brain tissue were significantly decreased than those in low dose(10 mg/kg)and high dose(30 mg/kg)resveratral treatment groups(P<0.01),the expres-sion level of SIRT1 mRNA was significantly increased than those in low dose(10 mg/kg)and high dose(30 mg/kg)resveratral treatment groups(P<0.01).Conclusion Resveratrol could play a neuroprotective role of cerebral ischemia-reperfusion injury in rats by allevi-ating the neuronal apoptosis.It may inhibit or reverse the cerebral ischemia-reperfusion nerve injury by activating the SIRT1 signaling pathway.

关 键 词：脑缺血再灌注损伤 白藜芦醇 神经元凋亡 沉默信息调控因子-1 脑梗死体积 脑组织含水量 Bax Caspase-3 

分 类 号：R743[医药卫生—神经病学与精神病学] R285.5[医药卫生—临床医学]