温阳振衰颗粒对慢性心力衰竭大鼠干预机制研究

Research on intervention mechanism of Wenyang Zhenshuai granule in treating chronic heart failure rats

目的:研究温阳振衰颗粒对慢性心力衰竭(CHF)大鼠外泌体微小RNA-21(miR-21)、心肌p38丝裂原活化蛋白激酶(p38MAPK)信号通路的影响。方法:取40只清洁级SD雄性大鼠作为研究对象,随机分为正常组、模型组、依那普利组、温阳振衰组,每组10只。正常组正常喂养,其他三组采用阿霉素诱导建立CHF模型。模型组、依那普利组、温阳振衰组分别给予0.9%氯化钠溶液、依那普利及温阳振衰颗粒灌胃处理。分别在灌胃前、灌胃完成后采血,提取外泌体,检测外泌体miR-21水平。在灌胃结束后4周处死大鼠,取心肌组织,检测p38MAPK和p-p38MAPK水平。结果:灌胃前,模型组、依那普利组、温阳振衰组LVEF低于正常组,E/A、LVDD、LVPW水平高于正常组,差异有统计学意义(均P<0.05)。灌胃后,温阳振衰组、依那普利组LVEF高于模型组,差异有统计学意义(均P<0.05)。灌胃后,温阳振衰组、依那普利组血清外泌体miR-21、心肌miR-21 mRNA高于模型组,差异有统计学(均P<0.05)。温阳振衰组、依那普利组p38MAPK和p-p38MAPK mRNA和蛋白水平低于模型组,差异有统计学意义(均P<0.05)。结论:温阳振衰颗粒治疗CHF效果较好,其机制可能与上调外泌体miR-21,抑制p38MAPK信号通路活性有关。

Objective:To study effect of Wenyang Zhenshuai granule on the signal pathway of microRNA-21(miR-21)in rat exosomes and p38 mitogen activated protein kinase(p38MAPK)in myocardium of rats with chronic heart failure(CHF).Methods:40 male SD rats of clean grade were selected as the research objects and divided into normal group,model group,enalapril group and Wenyang Zhenshuai group,10 rats in each group.The normal group was fed normally,the other three groups were induced by adriamycin to establish CHF model.The model group,enalapril group and Wenyang Zhenshuai group were given 0.9%sodium chloride solution enalapril and Wenyang Zhenshuai granules of gavage respectively.The blood samples were collected before and after gavage to extract exosomes and detect the level of miR-21.The rats were killed in the 4 weeks after the end of gavage and the myocardial tissue were taken p38MAPK and p-p38MAPK were detected.Results:The LVEF of model group,enalapril group and Wenyang Zhenshuai group were lower than that of the normal group before gastric lavaged.The E/A,LVDD and LVPW were higher than those in the normal group,difference statistically significant(all P<0.05).The LVEF of Wenyang Zhenshuai group and the enalapril group after gastric lavaged were higher than that in the model group,difference statistically significant(all P<0.05).The serum exosome miR-21 and miR-21 mRNA of myocardium after gastric lavaged in the Wenyang Zhenshuai group and the enalapril group were significantly higher than those in the model group,difference statistically significant(all P<0.05).The mRNA and protein levels of p38MAPK and p-p38MAPK in Wenyang Zhenshuai group and enalapril group were lower than those in the model group,difference statistically significant(all P<0.05).Conclusion:Wenyang Zhenshuai granule has reliable therapeutic effect on CHF and its mechanism may be related to up regulation of miR-21 in exosomes and inhibition of p38MAPK signaling pathway.