白藜芦醇通过调节SIRT1/AMPK信号通路对复发大鼠MCAO的神经保护作用机制研究  

Study of Neuroprotective Effects and Mechanism of RSV on Regulating the SIRT1/AMPK Signalling in Recurrent Ischemia Models in Rats

作　　者：王永久[1] 宫珍卿 程焱[2] Wang Yongjiu;Gong Zhenqing;Cheng Yan(Department of Neurology,The Eighth People's Hospital of Qingdao,Shandong 266100,China)

机构地区：[1]青岛市第八人民医院神经内科,266000 [2]天津医科大学总医院神经内科,300052

出　　处：《医学研究杂志》2019年第7期85-90,共6页Journal of Medical Research

基　　金：山东省青岛市卫生局基金资助项目(2013-WSZD065)

摘　　要：目的探讨白藜芦醇(resveratrol,RSV)通过调节SIRT1/AMPK信号通路对复发大鼠缺血性脑卒中的神经保护作用机制研究。方法成年雄性Wistar大鼠38只,采用微型动脉瘤夹夹闭法制作单次大脑中动脉栓塞(middle cerebral artery occlusion,MCAO,n=14)和双次MCAO模型(n=16),随机分为RSV治疗组和实验对照组,术后3天测定各组大鼠脑梗死体积并评价行为缺损的变化。另外8只大鼠为假手术组,随机分为RSV治疗组(n=5)和对照组(n=3)。采用Western blot法测定大鼠的SIRT1表达、AMPK、phospho-AMPK表达,去乙酰化荧光检测试剂盒进行SIRT1活性检测,ATP生物发光检测试剂盒测定ATP水平。结果与对照组比较,RSV显著改善神经行为功能(P<0.05),降低单次及双次MCAO大鼠脑梗死体积(P<0.05),提高缺血脑组织SIRT1及AMPK活性(P<0.05),SIRT1蛋白表达水平差异无统计学意义(P>0.05)。与对照组比较,RSV喂养3天后假手术组、单次MCAO组和双次MCAO组大鼠缺血脑组织ATP含量均显著增高(P<0.05),RSV使组织内ATP含量升高1.5~2.0倍。结论RSV对大鼠单次和双次MCAO模型均具有神经保护作用,RSV的神经保护作用与提高SIRT1及AMPK活性和增加脑缺血时能量需求有关。Objective To explore the neuroprotective mechanism of resveratrol (RSV) in a rat model of recurrent middle cerebral artery occlusion (MCAO) through the SIRT1/AMPK signalling pathway.Methods A total of 38 adult male wistar rats were subjected to once middle cerebral artery occlusion (MCAO)( n =14) and twice MCAO ( n =16) by placing an aneurysm microclip on the middle cerebral artery of the rat.Each model group was randomly divided into RSV treatment group and experimental control group.Cerebral infarction volume and behavioral defect were measured 3 days after operation in rats.The sham-operated group was randomly divided into RVS treatment group ( n =5) and control group ( n =3).The expressions of SIRT1,AMPK and phospho-AMPK were determined by Western blot analysis.The activity of SIRT1 was tested by a deacetylase fluorometric assays kit.ATP level was determined by a bioluminescence ATP detectionkit.Results Compared with the control group,RSV attenuated neurologic deficits ( P <0.05),decreased the cerebral infarction volume in once and twice MCAO rats ( P <0.05),increased the activity of SIRT1 and AMPK in ischemic brain tissue( P< 0.05),but there was no significant difference in the expression of SIRT1 ( P >0.05).After 3 days of RSV feeding,the content of ATP in ischemic brain tissue of rats in sham operation group,once MCAO group and twice MCAO group were significantly increased ( P< 0.05) compared with the control group.The content of ATP in tissue was increased by 1.5-2.0 times after RSV treatment compared with the control group.Conclusion RSV has neuroprotective effects on both once MCAO modelsand twiceMCAO models in rats.The neuroprotective effects of RSV is related to the increase of SIRT1 and AMPK activities and the increase of energy demand during cerebral ischemia.

关 键 词：白藜芦醇 神经保护 复发缺血脑卒中模型 SIRT1 AMPK 

分 类 号：R741[医药卫生—神经病学与精神病学]