天麻素经IRE1α/TRAF2/NF-κB通路调控大鼠急性心肌梗死诱导的炎性反应及机制研究

Regulatory effects of gastrodin on the inflammatory response induced by acute myocardial infarction in rats and its action mechanism via IRE1α/TRAF2/NF-κB pathway

目的探讨天麻素对大鼠急性心肌梗死(AMI)诱导的炎性反应的影响,并分析其作用机制。方法50只SD大鼠随机分为假手术(Sham)组、模型(AMI)组、天麻素低剂量(L-GAD)组、天麻素高剂量(H-GAD)组、卡托普利(CAP)组,每组10只。采用超声心动图检测大鼠心功能,TTC染色评估大鼠心肌梗死面积比,HE染色观察大鼠心肌组织病理形态学变化,ELISA法和qRT-PCR法分别检测大鼠血清及心肌组织中肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)、单核细胞趋化蛋白-1(MCP-1)含量及mRNA表达,Western blot法检测大鼠心肌组织中肌醇依赖性激酶1α(IRE1α)/肿瘤坏死因子受体相关因子2(TRAF2)/核因子(NF)-κB通路蛋白表达。结果与Sham组比较,AMI组大鼠心肌组织受损,存在明显心肌梗死,LVEF降低,LVDs和LVDd升高,血清和心肌组织中TNF-α、IL-6、MCP-1水平及mRNA表达升高,心肌组织中TRAF2蛋白表达量、p-IRE1α/IRE1α和p-p65/p65比值升高,差异均有统计学意义(P<0.05)。与AMI组比较,L-GAD、H-GAD组和CAP组大鼠心肌组织损伤减轻,心肌梗死面积比减小,LVEF升高,LVDs和LVDd降低,血清和心肌组织中TNF-α、IL-6、MCP-1水平及mRNA表达降低,心肌组织中TRAF2蛋白表达量、p-IRE1α/IRE1α和p-p65/p65比值下降,差异均有统计学意义(P<0.05)。结论天麻素可通过调控IRE1α/TRAF2/NF-κB通路减轻AMI大鼠心肌组织损伤及心肌梗死面积,改善大鼠心功能,抑制炎性反应。

Objective To investigate the regulatory effects of gastrodin on the inflammatory response induced by acute myocardial infarction(AMI)in rats and its action mechanism via IRE1α/TRAF2/NF-κB pathway.Methods Fifty SD rats were randomly divided into sham operation group,model(AMI)group,low-dose GAD group,high-dose GAD group and captopril(CAP)group,with 10 rats in each group.The cardiac function was measured by echocardiography,the area ratio of myocardial infarction was assessed by TTC staining,and the pathological changes of myocardial tissue were observed by HE staining,and the expression levels of TNF-α,IL6,MCP-1 mRNA in serum and myocardium were detected by ELISA and qRT-PCR,the expression levels of IRE1α/TRAF2/NF-κB pathway protein in rat myocardium were detected by Western Blot.Results Compared with those in sham operation group,the myocardial tissue damae and myocardial infarction in AMI group were more obvious,and LVEF levels were decreased,however,the expression levels of LVDS,LVDD,and TNF-α,IL-6,MCP-1 and mRNA in serum and myocardial tissue were significantly increased,and the expression levels of TRAF2 protein,the ratio of p-IRE1α/IRE1αand p-p65/p65 in myocardium tissue were significantly increased(P<0.05).Compared with those in AMI group,the myocardial injury degree and myocardial infarction ratio in low-dose GAD group,high-doae GAD group and CAP group were significantly decreased,and the LVEF levels were increased,however,the levels of LVDS and LVDD,and the expression levels of LVEF,TNF-α,IL-6,MCP-1 mRNA in serum and myocardium,and the expression levels of TRAF2 protein,the ratio of p-IRE1α/IRE1αand p-p65/p65 in myocardium tissue were significantly decreased(P<0.05).Conclusion Gastrodin can regulate IRE1α/TRAF2/NF-κB pathway to relieve the myocardial injury and myocardial infarction size,improve cardiac function and inhibit the inflammatory reaction in rats with AMI.