稳心颗粒对心肌梗死模型大鼠诱导性室性心动过速及心肌组织E6AP、C/EBPα表达的影响

Effect of Wenxin Granules(稳心颗粒) on Induced Ventricular Tachycardia and Expression of E6AP and C/EBPα in Myocardial Infarction Model Rats

目的探讨稳心颗粒治疗心肌梗死后室性心动过速(VT)的可能作用机制。方法结扎大鼠左冠状动脉前降支建立心肌梗死大鼠模型,将32只造模成功大鼠随机分为模型组、病毒干扰组、胺碘酮组和稳心颗粒组,另设正常组(正常饲养),假手术组(只穿线不结扎),每组8只。病毒干扰组术后第1、7天尾静脉注射2×1010 pfu E6相关蛋白(E6AP)干扰腺病毒;胺碘酮组术后第2天开始按照每次2.5 mg/kg予胺碘酮注射液腹腔注射,每天2次;稳心颗粒组给予稳心颗粒每次1.62 g/kg制成等体积混悬液2 ml灌胃;其余各组予2 ml蒸馏水灌胃,每日2次,持续7天。7天后采用颈外静脉进行静脉推注氯化钡0.4 mg/kg诱导VT,记录从给予氯化钡到出现VT的时间及持续时间;分别采用RT-PCR和免疫组化检测各组大鼠心肌组织E6AP、CCAAT或增强子结合蛋白α(C/EBPα)mRNA及蛋白的表达。结果与正常组和假手术组比较,模型组大鼠VT出现时间缩短,持续时间延长,心肌组织E6AP mRNA及蛋白表达降低,C/EBPαmRNA及蛋白表达升高(P<0.05)。与模型组比较,病毒干扰组大鼠VT出现时间缩短,持续时间延长,心肌组织E6AP mRNA及蛋白表达降低,C/EBPαmRNA及蛋白表达升高(P<0.05),而胺碘酮组和稳心颗粒组均可延迟VT出现时间,缩短持续时间,明显升高E6AP mRNA及蛋白表达,明显降低C/EBP mRNA及蛋白表达(P<0.05),胺碘酮组与稳心颗粒组各指标组间比较差异均无统计学意义(P>0.05)。结论稳心颗粒可能通过上调心肌梗死后心肌组织E6AP表达和抑制C/EBPα表达,从而提高心肌梗死后VT的出现阈值及缩短持续时间。

Objective To explore the possible action mechanism of Wenxin Granules(稳心颗粒)in the treatment of ventricular tachycardia(VT)after myocardial infarction.Methods A rat model of myocardial infarction was established by ligating the left anterior descending coronary artery in rats.A total of 32 successful rat models were randomly divided into a model group,a virus interference group,an amiodarone group and a Wenxin Granules group.A normal group(feed normally),sham operation group(only threaded without ligation)were set up,with 8 rats in each group.In the virus interfering group,2×1010 pfu E6-related protein(E6AP)was used to interfere with adenovirus on the 1st and 7th day after operation.The amiodarone group was intraperitoneally injected with 2.5 mg/kg amiodarone injection on the 2nd day after operation,2 times a day;Wenxin Granules were given to the Wenxin Granules group at a dose of 1.62 g/kg each time to make an equal volume of 2 ml of the suspension;The remaining groups were given 2 ml of distilled water 2 times a day for 7 days.Seven days later,VT was induced by intravenous bolus injection of strontium chloride 0.4 mg/kg,and the time and duration of VT from the administration of strontium chloride were recorded.RT-PCR and immunohistochemistry were used to detect E6AP,CCAAT or enhancer binding protein alpha(C/EBPα)mRNA and protein expression in each group.Results Compared with the normal group and the sham operation group,the VT appearance time of the model group shortened,the duration prolonged,the expression of E6AP mRNA and protein decreased,and the expression of C/EBPαmRNA and protein increased(P<0.05).Compared with the model group,the time of VT in the virus interfering group shortened,the duration prolonged,the expression of E6AP mRNA and protein decreased,and the expression of C/EBPαmRNA and protein increased(P<0.05).The amiodarone group and the Wenxin Granules group could delay the VT appearance time,reduce the duration,significantly increase the expression of E6AP mRNA and protein,and significantly reduce the expression of C/EBP mRNA and protein(P<0.05).There was no significant difference between the amiodarone group and the Wenxin Granules group(P>0.05).Conclusion Wenxin Granules may increase the expression of E6AP and inhibit the expression of C/EBPαin myocardial tissue after myocardial infarction,thereby increasing the threshold and decreasing duration of VT after myocardial infarction.