基于Notch通路研究蓟黄素对心肌缺血再灌注大鼠的心肌保护作用

Myocardial Protective Effect of Thistle on Myocardial Ischemia-Reperfusion Rats Based on Notch Pathway

目的探讨蓟黄素对心肌缺血再灌注大鼠Notch信号通路及心肌保护的作用。方法50只Wistar大鼠随机分为假手术组、心肌缺血再灌注大鼠模型组、蓟黄素组(灌胃100 mg/kg蓟黄素)、抑制剂组、蓟黄素+抑制剂组,每组10只。测定大鼠心律失常发生率、持续时间及大鼠左心室舒张末期压力(left ventricular end-diastolic pressure,LVEDP)、左心室收缩压(left ventricular systolic pressure,LVSP)、左心室内压力下降最大速率(left ventricular pressure drop,LV-dp/dtmax)、左心室内压力上升最大速率(left ventricular pressure rise,LV+dp/dtmax);染色法测定大鼠心肌梗死百分比;酶联免疫吸附测定(ELISA)法测定大鼠血清白细胞介素(interleukin,IL)-6、IL-10、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)及心肌组织中丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化酶(glutathione peroxidase,GSH-Px)浓度;实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction,RT-qPCR)法检大鼠心肌组织Notch1、Hes1 mRNA表达;蛋白质免疫印迹检测大鼠心肌组织Notch1、Hes1蛋白表达。结果与模型组相比,蓟黄素组大鼠心律失常发生率及持续时间、心肌梗死百分比、心功能、血清炎症因子、心肌组织MDA均降低,心肌组织SOD、GSH-Px及Notch1、Hes1蛋白及mRNA表达水平升高(P<0.05),Notch通路抑制剂可逆转蓟黄素对心肌缺血再灌注大鼠心肌的保护作用。结论蓟黄素通过激活Notch通路改善心肌缺血再灌注大鼠的心肌损伤。

Objectives To investigate the effect of thistle on Notch signaling pathway and myocardial protection in rats with myocardial ischemia-reperfusion.Methods Fifty Wistar rats were randomly divided into sham operation group,myocardial ischemia reperfusion rat model group,thistle group(gavage 100 mg/kg thistle),inhibitor group,and thistle+inhibitor group,with 10 rats in each group.The incidence and duration of arrhythmia in rats,left ventricular enddiastolic pressure(LVEDP),left ventricular systolic blood pressure(LVSBP),and the maximum rate of left ventricular pressure drop(LV-dp/dtmax),the maximum rate of left ventricular pressure rise(LV+dp/dtmax)were measured.The percentage of myocardial infarction was measured by staining.The concentrations of rat serum interleukin(IL)-6,IL-10,tumor necrosis factor-α(TNF-α)and malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in myocardial tissue were detected by enzyme linked immunosorbent assay(ELISA)method.The expressions of Notch1 and Hes1 mRNA in rat myocardial tissue were detected by real-time fluorescent quantitative polymerase chain reaction(RT-qPCR);the expressions of Notch1,Hes1 proteins were detected by Western blot(WB).Results Compared with those in model group,the incidence and duration of arrhythmia,the percentage of myocardial infarction,cardiac function,serum inflammatory factors and myocardial tissue MDA were lower in thistle group,the concentrations of SOD,GSH-Px and Notch1,Hes1 protein and mRNA expression levels were significantly higher(P<0.05).Notch pathway inhibitors can reverse the protective effect of thistle on myocardial ischemia-reperfusion in rats.Conclusions Thistle improves myocardial injury in rats with myocardial ischemia and reperfusion by activating Notch pathway.