温阳振衰颗粒对阿霉素诱导慢性心衰兔心肌细胞外信号调节激酶5表达的影响

Effects of Wenyang Zhenshuai Granule on the expression of extracellular signal-regulated kinase 5 of the myocardial tissue in rabbit model with chronic heart failure induced by adriamycin

目的观察温阳振衰颗粒对阿霉素诱导慢性心衰模型兔心肌细胞外信号调节激酶5表达的影响。方法健康新西兰兔60只,随机抽取15只为正常对照组,余45只兔耳缘静脉注射阿霉素4周后,先从中随机抽取13只为模型4周组,余下实验兔按心功能分层,随机分组,再随机分为模型8周组及各治疗组,各组用对应药物灌胃,连续4周。分别检测4、8周末兔心肌细胞外信号调节激酶5(ERK5)的总蛋白及蛋白磷酸化(P-ERK5)水平。结果阿霉素造模后,模型4、8周组心肌P-ERK5水平均下调,两者较正常对照组差异有统计学意义(P<0.05),且模型8周组较模型4周组下调更为明显(P<0.05);各组经药物干预4周后心肌P-ERK5水平较正常对照组仍明显下调(P<0.05),但均高于模型8周组(P<0.05),其中以阳性对照组和温阳高剂量组心肌P-ERK5水平升高最为明显(P<0.05);各组心肌ERK5水平相比差异无统计学意义。结论温阳振衰颗粒能上调ERK5蛋白磷酸化的水平,从而激活ERK5信号转导通路,其中以高剂量温阳振衰颗粒最为明显,这可能是其调控慢性心衰时心室重构和心肌细胞凋亡的重要机制之一。

Objective To elucidate the effects of Wenyang Zhenshuai Granule on the expression of extracellular signal-regulated kinase 5 （ERK5） of the myocardial tissue in rabbit model with chronic heart failure induced by adriamycin.Methods 15 rabbits were randomly extracted from 60 rabbits for the control group,13 rabbits were randomly extracted from other 45 rabbits after modeled by intravenous injection of adriamycin for 4 weeks,which is named model 4 weeks group.The rest rabbits were randomly divided into 5 groups including the model 8 weeks group and the 4 medicine treatment groups.Each medicine group was given enalapril （positive control） or Wenyang Zhenshuai Granule high dose,medium dose and low dose by gastric administration for 4 consecutive weeks.The expression levels of ERK5 and P-ERK5 in all groups were detected by western blotting.Results P-ERK5 expression levels in myocardial tissue of model 4 and 8 weeks groups were lower than that in control group （P＜0.05）,and its down-regulation in model 8 weeks group was marked than that of model 4 weeks group.4 weeks after treatment,P-ERK5 expression levels in all medicine treating groups were lower than that of control group,but significantly higher than that of model 8 weeks group （P＜0.05）.Among of them,up-regulation of P-ERK5 in the positive control group and Wenyang Zhenshuai Granule high dose group were more obviously （P＜0.05）.There were no significant differences in ERK5 proteins among these groups.Conclusion Wenyang Zhenshuai Granule can promote the level of p-ERK5 protein,then activate ERK5 signal transduction pathway,and Wenyang Zhenshuai Granule high dose group has more significant effects than other two doses groups,which may be one of the mechanisms of Wenyang Zhenshuai Granule regulating the ventricular remodeling and the apoptosis of myocardial cells in chronic heart failure.