| 魏毅君,翟蒙恩,王晓武,路志红,金振晓,赵振伟.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[J].现代生物医学进展英文版,2017,17(17):3216-3219. |
| 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 |
| Received:December 10, 2016 Revised:December 30, 2016 |
| DOI：10.13241/j.cnki.pmb.2017.17.004 |
| 中文关键词: 姜黄素 脑缺血再灌注损伤 凋亡 氧化应激 SIRT1 FOXO1 |
| 英文关键词: Curcumin Cerebral ischemia reperfusion injury Apoptosis Oxidative stress SIRT1 FOXO1 |
| 基金项目:国家自然科学基金项目（81671136；81570231） |
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| 中文摘要: |
| 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。 |
| 英文摘要: |
| ABSTRACT 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 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 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 in- farct volume, Complex I activity, reactive oxygen species (ROS) production and the expression levels of 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 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. Conclusion: Our results demonstrate that curcumin pretreatment attenuates cere- bral IRI by reducing IR-induced oxidative stress and apoptosis through the activation of SIRT1/FOXO1 signaling pathway. |
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