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白藜芦醇通过Sirtuins 1通路促进自噬减轻大鼠脑缺血/再灌注损伤 被引量:16

Resveratrol alleviates cerebral ischemia-reperfusion injury by promoting autophagy through Sirtuins1 pathway in rats
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摘要 目的观察白藜芦醇(Res)在大鼠局灶性脑缺血/再灌注(I/R)损伤中脑保护作用与自噬的关系。方法随机将大鼠分成假手术组(S组)、脑缺血/再灌注模型组(I/R组)、低和高剂量(15和40 mg/kg)Res处理组(R1和R2组),其中将R2组另设2个亚组:R2+3-甲基腺嘌呤(3-MA)组和R2+Sirt1抑制剂Sirtinol组。线栓法构建大鼠I/R模型。缺血2 h,再灌注24 h后,用尼氏染色观察皮质区的组织学形态;用2,3,5-氯化三苯基四氮唑(TTC)染色法检测脑组织的梗死体积;用real-time QPCR和Western blot检测脑组织中Sirt1和LC3的mRNA和蛋白表达。结果与S组相比,I/R组大鼠可见明显的脑梗死灶,显微镜下见病理损伤改变,自噬相关蛋白LC3Ⅱ/LC3Ⅰ、Sirt1表达均有上升。Res预处理后,能明显减轻I/R大鼠皮质区的病理损伤,减少脑梗死体积(P<0.01),显著增加I/R大鼠脑组织中LC3Ⅱ/LC3Ⅰ和Sirt1的表达(P<0.01);而Sirt1抑制剂及3-MA能削弱Res的作用。结论 Res减轻大鼠局灶性脑缺血/再灌注损伤的脑保护作用可能与Res通过提高Sirt1的表达进而促进自噬来完成的。 Objective To observe the potential roles of autophagy induced by Resveratrol(Res) in rats model of fo- cal cerebral ischemia-reperfusion(I/R)injury. Methods Rats were randomly divided into sham-operated group(S group), cerebral ischemia-reperfusion group (I/R group), low and high dose of Res pretreatment (15 and 40 mg/kg) group (R1 and R2 group) ; and R2 group were randomly sub-divided into R2 +3-MA group and R2 + Sirtinol group. The focal cerebral isehemia-reperfusiong (I/R) rat models were established by the middle cerebral artery occlusion (MCAO) using intraluminal suture method. Nissl's staining was used to observe the pathological changes of brain tissue ; 2, 3, 5-triphenyltetrazolium chloride ( TYC ) straining was used to observe infarct volume ; real-time QPCR and Western blot assessments were performed to analyse the mRNA and protein expression of micro- tubule-associated protein light chain 3 (LC3) and mammalian sir2-related protein 1 (Sial), respectively. Results Compared with S group,I/R group showed obvious focal cerebral infarct, pathological damage change and autophagyrelated protein LC3 II/LC3 I , Sirtl expression increased. Res pretreatment can significantly alleviate the patho- logical injury of rat cortical area, reduce the infarction volume (P 〈 0. 01 ) and increase the expression of LC3 11 / LC3 I and Sirtl (P 〈0. 01 ); while the Sirtl inhibitor and 3-MA can weaken the effect of Res. Conclusions Resveratrol enhances autophagy through activation of SIRT1 pathway and autophagy induction plays an important role in the neuroprotection of resveratrol in rats model of focal cerebral ischemia-reperfusion(L/R) injury.
出处 《基础医学与临床》 CSCD 2015年第4期496-501,共6页 Basic and Clinical Medicine
基金 重庆市科技攻关计划项目(2008AB5118)
关键词 脑缺血/再灌注损伤 白藜芦醇 自噬 沉默信息调控因子1 cerebral ischemia/reperfusion injury resveratrol autophagy sirtuinsl
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