舒芬太尼后处理对大鼠心肌缺血再灌注损伤时 Nrf2-ARE 信号通路的影响

Effect of Sufentanil postconditioning on Nrf2-ARE signaling pathway during myocardial ischemia-reperfusion injury of rats

摘要:

目的 探讨舒芬太尼后处理对大鼠心肌缺血再灌注损伤时Nrf2-ARE 信号通路的影响。方法 30 只健康雄性SD 大鼠随机分为假手术组、缺血再灌注组及舒芬太尼后处理组，复制大鼠心肌缺血再灌注损伤 模型，舒芬太尼后处理组于再灌注前5 min，按1μg/kg 的剂量将舒芬太尼经股静脉注入，假手术组和缺血再 灌注组则注入等量的生理盐水，检测3 组大鼠心肌梗死面积以及病理学改变，检测3 组大鼠心肌细胞凋亡情况， 利用实时荧光定量PCR（qRT-PCR）和Western blot 分别检测3 组大鼠心肌组织中Nrf2、HO-1、NQO1、 SOD1 及GSTM2 基因和蛋白表达。结果 与假手术组比较，缺血再灌注组和舒芬太尼后处理组大鼠心肌细胞凋 亡指数和梗死面积均增加，与缺血再灌注组比较，舒芬太尼后处理组大鼠心肌细胞凋亡指数和梗死面积均降 低（P <0.05）；与假手术组比较，缺血再灌注组和舒芬太尼后处理组大鼠心肌组织中Nrf2、HO-1、NQO1、 SOD1 及GSTM2 基因和蛋白相对表达量均降低（P <0.05）；与缺血再灌注组比较，舒芬太尼后处理组大鼠心肌 组织中Nrf2、HO-1、NQO1、SOD1 及GSTM2 基因和蛋白相对表达量均升高（P <0.05）。结论 舒芬太尼 后处理可有效减轻缺血再灌注损伤大鼠心肌梗死面积以及细胞凋亡，其机制可能通过激活Nrf2/ARE 信号通路 促使其下游Ⅱ相解毒酶及抗氧化酶的表达，从而有效对抗氧化应激损伤。

Abstract:

Objective To investigate the effect of Sufentanil postconditioning on Nrf2-ARE signaling pathway during myocardial ischemia-reperfusion injury of rats. Methods Thirty healthy male SD rats were randomly divided into sham-operation group, ischemia-reperfusion group and Sufentanil postconditioning group. The rat models of myocardial ischemia-reperfusion injury were prepared. In the Sufentanil postconditioning group, Sufentanil was injected into femoral vein 5 min before reperfusion at a dose of 1 μg/kg, the rats in the sham operation group and the ischemia-reperfusion group were injected with the same amount of normal saline. The myocardial infarct sizes and pathologic changes in three groups were detected. The cardiomyocyte apoptosis in the three groups was detected. The expressions of Nrf2, HO-1, NQO1, SOD1 and GSTM2 genes and proteins were detected by qRT-PCR and Western blot, respectively. Results Compared with the sham-operation group, the cell apoptotic indexes and the myocardial infarct sizes in the ischemia-reperfusion group and the Sufentanil postconditioning group were increased (P < 0.05). Compared with the ischemia-reperfusion group, the cell apoptotic index and the myocardial infarct size in the Sufentanil postconditioning group were significantly decreased (P < 0.05). Compared with the sham-operation group, the relative expression levels of Nrf2, HO-1, NQO1, SOD1 and GSTM2 genes and proteins in the ischemiareperfusion group and the Sufentanil postconditioning group were significantly decreased (P < 0.05). Compared with the ischemia-reperfusion group, the relative expression levels of Nrf2, HO-1, NQO1, SOD1 and GSTM2 genes and proteins in the Sufentanil postconditioning group were increased, the differences were statistically significant (P < 0.05). Conclusions Sufentanil postconditioning could effectively reduce the myocardial infarct size and cell apoptosis in the rats with ischemia-reperfusion injury. The mechanism might be through the activation of Nrf2/ARE signaling pathway to promote the expressions of the downstream phase II detoxification enzymes and antioxidant enzymes, and thus effectively resist oxidative stress injury.