目的 研究大鼠脑缺血再灌注损伤后沉默信息调节因子1(SIRT1)对缺血脑组织周边炎性反应的影响及其与核转录因子-KB(NF-kB)通路的关系.方法 选择健康雄性 SD大鼠40只,随机均分为4组:假手术组、模型组、白藜芦醇组、EX527组.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NF-kB mR-NA含量及蛋白表达变化.于1、3、7、14 d对大鼠进行神经功能缺损评分.结果 白藜芦醇组3、7、14 d神经功能缺损评分明显低于模型组和EX527组(P＜0. 01).白藜芦醇组 NF-KB、IL-1β、IL-6、TNF-α mRNA及蛋白表达量明显低于模型组和EX527组(P＜0.01);SIRT1明显高于模型组和 EX527组(P＜0.01).结论 SIRT1的激活可促进脑缺血再灌注大鼠的神经功能缺损恢复,减轻炎性反应,其机制可能与NF-KB通路有关.%Objective To investigate the role of silent information regulator protein 1 (SIRT1) in inflammatory reaction in peri-ischemic brain tissue after ischemia reperfusion injury in rats and its relationship with nuclear factor-K-gene binding (NF-kB) pathway. Methods Forty healthy male SD rats were randomly divided into sham group, I/R group, Res + I/R group and EX527 + I/R group (10 in each group). The expression levels of interleukin(IL)-1β, IL-6, tumor necrosis factor-a(TNF-a), SIRT1 and NF-kB in peri-ischemic brain tissues were detected using Western blot and RT-PCR respectively. Neurological severity score(NSS) were measured 1 d, 3 d, 7 d and 14 d after reperfusion. Results NSS in Res + I/R group in 3, 7, 14 day after reperfusion was significantly lower than those of I/R group and EX527 + I/R group (P ＜0. 01); Compared with I/R and EX527 + I/R group, the peri-ischemic brain tissue mRNA expression and the protein expression of NF-kB, IL-1 β, IL-6 and TNF-a were significantly decreased in Res + I/R group. SIRT1 was significantly increased (P ＜ 0. 01). Conclusion The activation of SIRT1 can improve cerebral ischemic damage and reduce inflammatory reaction in rats. Its mechanism may be related to the NF-kB pathways.
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