姜黄素后处理通过SIRT1/FOXO1信号通路拮抗小鼠脑缺血苒灌注损伤. (Chinese)

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 ischemia reperfusion (IR) injury (IRI) in adult mice. Methods: In this study, adult mice were subjected to 30 min of ischemia and 24h 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 intraperitoneally administrated following reperfusion with a single dose of 100 mg/kg. 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 infarct volume, Complex I activity, reactive oxygen species (ROS) production and the expression levels o f SIRT1, Ac-FOXO1, Bax, Bcl-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 infarct 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 SIRT 1 /FOXO1 signaling pathway. [ABSTRACT FROM AUTHOR]

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30min,再灌注24h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24h检测脑梗体积、ComplexI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ComplexI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。 [ABSTRACT FROM AUTHOR]

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