姜黄素后处理通过SIRT1/FOXO1信号通路拮抗小鼠脑缺血再灌注损伤  

Curcumin Posttreatment Ameliorates Cerebral Ischemia Reperfusion Injury of Mice through Activating SIRT1/FOXO1 Signaling Pathway

作　　者：魏毅君[1] 翟蒙恩[2] 王晓武[2] 路志红[3] 金振晓[2] 赵振伟[1] 

机构地区：[1]第四军医大学唐都医院神经外科,陕西西安710000 [2]第四军医大学西京医院心血管外科,陕西西安710032 [3]第四军医大学西京医院麻醉科,陕西西安710032

出　　处：《现代生物医学进展》2017年第17期3216-3219,共4页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(81671136;81570231)

摘　　要：目的:探究姜黄素后处理是否通过激活SIRT1/FOXO1信号通路抵抗小鼠脑缺血再灌注损伤。方法:小鼠脑缺血30 min,再灌注24 h建立脑缺血再灌注模型。手术前脑室内注射SIRT1特异性抑制剂EX527。再灌注后腹腔注射姜黄素。小鼠随机分为以下6组:假手术组;单纯姜黄素后处理组;缺血再灌注组;缺血再灌注+姜黄素后处理组;EX527预处理+缺血再灌注+姜黄素后处理组;EX527预处理+脑缺血再灌注组。再灌注24 h检测脑梗体积、Complex I活性、ROS含量以及SIRT1、Ac-FOXO1、Bax、Bcl-2、Caspase-3蛋白表达情况。结果:与手术组相比,姜黄素后处理组梗死区脑组织SIRT1的表达量及活性明显增加,脑梗体积降低,ROS含量降低而Complex I活性增高,Bcl-2的表达增高而Bax和Caspase-3的表达量降低(均P<0.05)。阻断SIRT1信号通路后上述姜黄素脑保护作用均减弱(P<0.05)。结论:我们的研究首次证实姜黄素后处理通过激活SIRT1/FOXO1信号通路,进而降低氧化应激与凋亡,最终减轻脑缺血再灌注损伤。Objective： To elucidate the definite role of silent information regulator 1 （SIRT1）/Forkhead box protein O1 （FOXO1） signaling pathway in the protective effect of curcumin posttreatment against cerebral isehemia reperfusion （IR） injury （IRI） in adult mice. Methods： In this study, adult mice were subjected to 30 min of ischemia and 24 h of reperfusion to mimic the cerebral IRI. Prior to this procedure, the mice were given intracerebroventricularly with or without a SIRT1 selective inhibitor, EX527. Curcumin was intraperi- toneally administrated following reperfusion with a single dose of 100 ms/ks. The mice were randomly divided into six groups： Sham group, Cur group, IR group, IR＋Cur group, IR＋Cur＋EX527 group and IR＋EX527 group. Twenty-four hours after the reperfusion, the in- farct volume, Complex I activity, reactive oxygen species （ROS） production and the expression levels of SIRT1, Ac-FOXO1, Bax, Bet-2 and Caspase-3 in each group were measured. Results： Compared with the IR group, curcumin posttreatment significantly increased the expression level of SIRT1, as well as its deacetylase activity. Curcumin conferred a cerebral-protective effect, as shown by reduced in- farct volume compared with the IR group. In addition, curcumin posttreatment caused a significant upregulation of Complex I activity and downregulation of ROS production. Moreover, curcumin posttreatment increased the expression level of an anti-apoptotic factor, Bcl2, and decreased the expression level of the pro-apoptotic factor Bax and Caspase-3. However, these cerebral-protective effects of curcumin were largely abolished by EX527 treatment. Conclusions： Our results demonstrate that curcumin pretreatment attenuates cerebral IRI by reducing IR-induced oxidative stress and apoptosis through the activation of SIRT1/FOXO1 signaling pathway.

关 键 词：姜黄素 脑缺血再灌注损伤 凋亡 氧化应激 SIRT1 FOX01 

分 类 号：R743.3[医药卫生—神经病学与精神病学]