白藜芦醇通过SIRT1/FoxO1路径改善大鼠脑缺血/再灌注损伤机制研究  

Resveratrol improves the cerebral ischemia-reperfusion injury in rats through the SIRT1/ FoxO1 signal pathway

作　　者：曹自为 李传文 刘学春[1,2] 管叶明[1,2] 汪青松[1,2] Cao Ziwei;Li Chuanwen;Liu Xuechun(Clinical College of Chinese PLA,Anhui Medical University,Hefei 230031;Dept of Neurology,105th Hospital of Chinese PLA,Hefei 230031)

机构地区：[1]安徽医科大学解放军临床学院,合肥230031 [2]解放军第105医院神经内科,合肥230031

出　　处：《安徽医科大学学报》2019年第5期719-723,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81171108);2015年度军区医学科技创新课题基金(编号:15MS047)

摘　　要：目的研究白藜芦醇(RES)通过沉默信息调节因子1/叉头转录因子O1(SIRT1/FoxO1)路径改善大鼠脑缺血/再灌注(CIR)损伤的机制。方法 40只SD大鼠随机分为4组,假手术(Sham)组、模型(CIR)组、白藜芦醇(RES)组,白藜芦醇(RES)+SIRT1抑制剂(EX527)组,采用改良线栓法构建大鼠右侧大脑中动脉栓塞模型,采用逆转录-聚合酶链反应(RT-PCR)法和Western blot法检测各组大鼠脑组织匀浆中白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α、SIRT1及核转录因子(NF)-κB mRNA含量及蛋白表达变化。选择1、3、7、14 d四个时间点参照改良神经损伤严重程度评分(mNSS)量表对大鼠神经功能缺损进行评分。结果 RES组3、7、14 d神经功能缺损评分明显低于CIR组和RES+EX527组(P<0.01)。RES组FoxO1、IL-1β、IL-6、TNF-αmRNA及蛋白表达量明显低于CIR组和RES+EX527组(P<0.01),而RES组SIRT1 mRNA及蛋白表达量明显高于CIR组和RES+EX527组(P<0.01)。结论 RES可通过SIRT1/FoxO1路径降低炎症因子TNF-α、IL-1β释放和促进抗凋亡因子B淋巴细胞瘤-2(Bcl-2)的表达,从而改善大鼠CIR损伤。Objective To investigate the protective effect of resveratrol(resveratrol,RES) on cerebral ischemia/reperfusion(CIR) injury in rats and its relationship with sirtuin- 1/forkhead transcription factor O1(SIRT1/FoxO1) pathway. Methods Forty SD rats were randomly divided into 4 groups: sham group,model(CIR) group,resveratrol(RES) group,resveratrol(RES)+EX527 group. The model of right middle cerebral artery occlusion was established in rats. Reverse transcription- polymerase chain reaction(RT-PCR) and Western blot were used to detect interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-α,SIRT1 and NF-κB mRNA content and protein expression changes in brain homogenate of each group. Rats with neurological deficits were scored by reference to the mNSS scale at four time points,1 d,3 d,7 d, and 14 d. Results The neurological deficit scores of the RES group were significantly lower than those of the CIR group and the RES+EX527 group( P <0.01). The mRNA and protein expressions of FoxO1,IL-1β,IL-6 and TNF-α in RES group were significantly lower than those in CIR group and EX527 group( P <0.01),while the expression of SIRT1 mRNA and protein in RES group was significantly higher than that in CIR group and RES+EX527 group( P <0.01). Conclusion Resveratrol can inhibit the expression of FoxO1,reduce the release of inflammatory factors TNF-α,IL-1β and promote the expression of anti-apoptotic factor Bcl-2 by activating SIRT1,thereby improving cerebral ischemia/reperfusion damage in rats.

关 键 词：白藜芦醇 缺血再灌注损伤 SIRT1 FOXO1 

分 类 号：R743.3[医药卫生—神经病学与精神病学]