SIRT1/PGC-1α信号通路在大鼠血管性认知损伤中的作用及分子机制  

Role and molecular mechanism of SIRT1/PGC-1αsignaling pathway in vascular cognitive impairment in rats

作　　者：陈罕[1,2] 孙肖爽[1] 李红杰[1] 韦红伟 徐忠信[2] CHEN Han;SUN Xiaoshuang;LI Hongjie;WEI Hongwei;XU Zhongxin(Department of Neurology,Changchun Central Hospital,Changchun 130051,China;不详)

机构地区：[1]长春市中心医院神经内科,长春130051 [2]吉林大学中日联谊医院神经内科 [3]长春中医药大学临床医学院

出　　处：《山东医药》2021年第29期38-42,共5页Shandong Medical Journal

基　　金：吉林省科技发展计划项目(20200703008ZP)。

摘　　要：目的分析沉默信息调节因子2相关酶1/过氧化物酶体增殖物激活受体γ共激活因子1(SIRT1/PGC-1α)信号通路在大鼠血管性认知损伤中的作用并探讨其分子机制。方法选取2~3月龄Wistar大鼠,随机分为假手术组、模型组、激活组、联合组各7只,抑制组6只。除假手术组外,各组均采用改良版双侧颈总动脉永久性结扎法建立慢性脑缺血模型。激活组、联合组术后每天腹腔注射SIRT1激活剂白藜芦醇50 mg/kg,联合组、抑制组每天向大鼠侧脑室内注射SIRT1去乙酰化抑制剂EX-5275µL,假手术组、模型组腹腔注射等量25%二甲基亚砜,连续给药6周。采用Morris水迷宫试验观察大鼠认知功能,免疫组化染色法、Western blotting法检测大鼠海马CA1区SIRT1、PGC-1α蛋白表达,qRT-PCR法检测SIRT1、PGC-1αmRNA表达,ELISA法检测氧化应激指标超氧化物歧化酶(SOD)、丙二醛(MDA)表达。结果与假手术组比较,模型组逃避潜伏期增长、目标象限停留时间减少,SIRT1、PGC-1α蛋白表达减少,SOD表达减少、MDA表达增加。与模型组比较,激活组逃避潜伏期减少、目标象限停留时间增长,SIRT1、PGC-1α蛋白表达增加,SOD表达增加而MDA表达减少;抑制组逃避潜伏期增长、目标象限停留时间减少,PGC-1α蛋白表达减少,SOD表达减少而MDA表达增加;联合组逃避潜伏期增长、目标象限停留时间减少,SIRT1蛋白表达增加、PGC-1α蛋白表达减少,MDA表达增加(P均<0.05)。各组SIRT1、PGC-1αmRNA表达比较差异均无统计学意义。结论激活SIRT1/PGC-1α信号通路可改善慢性脑缺血引起的大鼠血管性认知损伤,该作用可能与对抗氧化应激有关。Objective To detect the effect of regulation of silent information regulator 2-related enzyme 1(SIRT1)/peroxisome proliferator-activated receptor-gamma co-activator-1α(PGC-1α)signaling pathway on vascular cognitive im⁃pairment and its possible mechanism.Methods Wistar rats aged 2-3 months were randomly divided into the sham-operated group(n=7),model group(n=7),activated group(n=7),combined group(n=7),and inhibited group(n=6).Model of chronic cerebral ischemia was established by permanent ligation of bilateral common carotid arteries(2-VO)in each group except for sham-operated group.Resveratrol was administered intraperitoneally to rats of the activated group and combined group at a dose of 50 mg/kg per day.The rats in the combined group and the inhibited group were injected with SIRT1 deacetylation inhibitor EX-527 into the lateral ventricle of rats daily at a dose of 5 μL every day.In the sham-operated group and model group,the rats were injected with equal amount of 25%dimethyl sulfoxide as control.All drugs used above lasted for 6 weeks continuously.Cognitive impairment was assessed by Morris water maze test.The protein expres⁃sion levels of SIRT1 and PGC-1αin CA1 region of rat hippocampus were detected by immunohistochemical staining and Western blotting,and their mRNA expression levels were detected by qRT-PCR.The expression levels of superoxide dis⁃mutase(SOD)and malondialdehyde(MDA),as indicators of oxidative stress,were measured by ELISA.Results Compared with the sham-operated group,the model group showed increased escape latency,decreased time of staying in target quadrant,decreased SIRT1 and PGC-1αprotein expression and SOD expression,and increased MDA expression.Compared with the model group,the activated group showed decreased escape latency,increased target quadrant staying time,enhanced SIRT1 and PGC-1αprotein expression,increased SOD expression and decreased MDA expression;the inhibited group showed increased escape latency and MDA expression,decreased target quadrant staying time,PGC-1

关 键 词：慢性脑缺血 血管认知性损伤 SIRT1蛋白 PGC-1α蛋白 氧化应激 

分 类 号：R183.3[医药卫生—流行病学]