远隔缺血预适应通过AMPK/PGC-1α信号通路促进线粒体生物合成保护脑缺血再灌注损伤大鼠  

Remote ischemic preconditioning promotes mitochondrial biosynthesis and protects cerebral ischemia-reperfusion injury in rats via AMPK/PGC-1αsignaling pathway

作　　者：张雷[1] 袁伟琼 孔祥丽[1] 李军朝[1] 张蓓[1] Zhang Lei;Yuan Weiqiong;Kong Xiangli;Li Junchao;Zhang Bei(Department of Neurology,the First Affiliated Hospital of Xi’an Medical University,Xi’an 710000,China;Department of General Surgery,the Second Affiliated Hospital of Xi’an Jiao tong University,Xi’an 710000,China)

机构地区：[1]西安医学院第一附属医院神经内科,西安710000 [2]西安交通大学第二附属医院普通外科,西安710000

出　　处：《国际脑血管病杂志》2022年第6期426-432,共7页International Journal of Cerebrovascular Diseases

基　　金：陕西省教育厅科研计划项目(21JK0899)。

摘　　要：目的探讨远隔缺血预处理(remote ischemic preconditioning,RIPC)对大鼠脑缺血再灌注(ischemic reperfusion,I/R)损伤的保护机制。方法将48只SD大鼠随机分为假手术组、RIPC组、I/R组、RIPC+I/R组和compound C组,每组9只。测定大鼠神经功能评分、脑梗死体积(TCC染色)和神经元凋亡率(TUNEL染色),检测脑组织均浆内超氧化物歧化酶(superoxide dismutase,SOD)2活性和丙二醛水平,蛋白质印迹法检测脑组织中AMP活化蛋白激酶(AMP-activated protein kinase,AMPK)/过氧化物酶体增殖物激活受体γ辅激活因子(peroxisome proliferator-activated receptor-γcoactivator,PGC)-1α信号通路相关蛋白表达水平。结果I/R组神经功能缺损评分、脑梗死体积和神经元凋亡率显著高于假手术组(P均<0.05);与I/R组相比,RIPC+I/R组神经功能缺损评分、脑梗死体积和神经元凋亡率均显著降低(P均<0.05);与RIPC+I/R组相比,compound C组神经功能缺损评分、脑梗死体积和神经元凋亡率显著增高(P均<0.05)。与假手术组相比,I/R组SOD活性显著降低,丙二醛含量显著增高(P均<0.05);与I/R组相比,RIPC+I/R组SOD活性显著增高,丙二醛含量显著降低(P均<0.05);与RIPC+I/R组相比,compound C组SOD活性显著降低,丙二醛含量显著增高(P均<0.05)。与假手术组相比,I/R组脑组织AMPK、p-AMPK、PGC-1α、核呼吸因子(nuclear respiratory factor,NRF)-1、线粒体转录因子A(mitochondrial transcription factor A,TFAM)、SOD2、解偶联蛋白2(uncoupling protein 2,UCP2)、细胞色素c(cytochrome c,CytC)、凋亡诱导因子(apoptosis-inducing factor,AIF)表达均显著增高(P均<0.05);与I/R组相比,RIPC+I/R组缺血脑组织AMPK、p-AMPK、PGC-1α、NRF-1、TFAM、SOD2、UCP2表达显著增高,CytC和AIF表达显著降低(P均<0.05);与RIPC+I/R组相比,compound C组脑组织AMPK、p-AMPK、PGC-1α、NRF-1、TFAM、SOD2、UCP2表达显著降低,CytC和AIF表达显著增高(P均<0.05)。结论RIPC对I/R损伤具有保护作用,其机制可能与Objective To investigate the protective mechanism of remote ischemic preconditioning(RIPC)on cerebral ischemia-reperfusion(I/R)injury in rats.Methods Forty-eight SD rats were randomly divided into sham operation group,RIPC group,I/R group,RIPC+I/R group,and compound C group(n=9 in each group).The neurological function score,cerebral infarction volume(TCC staining)and neuronal apoptosis rate(TUNEL staining)were measured.The activity of superoxide dismutase(SOD)2 and malondialdehyde level in homogenate of brain tissue were detected.Expression levels of AMP-activated protein kinase(AMPK)/peroxisome proliferator-activated receptor-γcoactivator(PGC)-1αsignaling pathway-related proteins in brain tissue were detected by Western blot.Results The neurological deficit score,cerebral infarction volume and neuron apoptosis rate in the I/R group were significantly higher than those in the sham operation group(all P<0.05).Compared with the I/R group,the neurological deficit score,cerebral infarction volume and neuron apoptosis rate in the RIPC+I/R group were significantly decreased(all P<0.05).Compared with the RIPC+I/R group,the neurological deficit score,cerebral infarction volume and neuron apoptosis rate in the compound C group were significantly increased(all P<0.05).Compared with the sham operation group,the SOD activity in the I/R group was significantly decreased,and the malondialdehyde content was significantly increased(all P<0.05).Compared with the I/R group,the SOD activity in the RIPC+I/R group was significantly increased,and the malondialdehyde content was significantly decreased(all P<0.05).Compared with the RIPC+I/R group,the SOD activity in the compound C group was significantly decreased,and the malondialdehyde content was significantly increased(all P<0.05).Compared with the sham operation group,the expressions of AMPK,p-AMPK,PGC-1α,nuclear respiratory factor(NRF)-1,mitochondrial transcription factor A(TFAM),SOD2,uncoupling protein 2(UCP2),cytochrome C(CytC),and apoptosis-inducing factor(AIF)in the brain

关 键 词：脑缺血 再灌注损伤 缺血预处理 AMP-活化蛋白激酶 过氧化物酶体增殖物激活受体γ共激活因子1-α 信号转导 神经保护药 大鼠 

分 类 号：R743.3[医药卫生—神经病学与精神病学]