基础医学与临床 ›› 2015, Vol. 35 ›› Issue (4): 496-501.

• 研究论文 • 上一篇    下一篇

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

石瑶,郭倩,周也涵,万丹,叶秀峰   

  1. 重庆医科大学
  • 收稿日期:2014-09-25 修回日期:2014-12-26 出版日期:2015-04-05 发布日期:2015-04-08
  • 通讯作者: 叶秀峰 E-mail:yxf1960@126.com
  • 基金资助:
    重庆市科技攻关计划项目

Resveratrol alleviates cerebral ischemia-reperfusion injury by promoting autophagy through Sirtuins1 pathway in rats

  • Received:2014-09-25 Revised:2014-12-26 Online:2015-04-05 Published:2015-04-08

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LC3 II/LC3 I、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LC3 II/LC3 I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。

关键词: 关键词:脑缺血/再灌注损伤, 白藜芦醇, 自噬, Sirt1

Abstract: Objective To observe the potential roles of autophagy induced by Resveratrol(Res) in rats model of focal 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 ischemia-reperfusiong (I/R) rats 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 (TTC) straining was used to observe infarct volume; Real-time QPCR and Western blot assessments were performed to analyse the mRNA and protein expression of microtubule-associated protein light chain 3 (LC3) and mammalian sir2-related protein 1 (Sirt1), respectively. Results Compared with S group,I/R group showed obvious focal cerebral infarct,pathological damage change and autophagy related protein LC3 II/LC3 I, Sirt1 expression increased. Res pretreatment can significantly alleviate the pathological injury of rat cortical area, reduce the infarction volume (P<0.01) and increase the expression of LC3 II/LC3 I and Sirt1 (P<0.01); while the Sirt1 inhibitor and 3-MA can weaken the effect of Res. Conclusions Resveratrol enhance 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(I/R)injury.

Key words: Key Words: Cerebral ischemia/reperfusion injury, Resveratrol, Autophagy, Sirt1

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