扶阳强心方通过调节ERK1/2信号通路改善CHF血流动力参数

Fuyang Qiangxin Decoction Improves Hemodynamic Parameters by Adjusting ERK1/2 Signaling Pathway in CHF Rabbit Models

目的：研究扶阳强心方对兔CHF模型血流动力学变化和ERK1/2信号通路调节的影响。方法：将新西兰大白兔40只随机等分为耳缘注射阿霉素并扶阳强心方组（A）、耳缘注射阿霉素并地高辛组（B）、耳缘注射阿霉素组（C）、正常对照组（D）共4组,A、B、C组采用注射阿霉素的方法构建CHF模型,D组不做任何处理。造模后第14天开始给药,A组用扶阳强心方中药浸膏溶液（12 m L·kg^（-1）·d^（-1））灌胃,B组用地高辛（1.25μg·m L^（-1）·d^（-1））灌胃,C、D组分别给予等量生理盐水灌胃。以上各组连续灌胃30 d后行超声心动图观察其血流动力学变化,苏木素-伊红（HE）染色观察各组组织形态学差异,RT-PCR与Western blot分别检测ERK1/2mRNA和蛋白表达。结果：与C组相比较,A和B组LVSD、LVDD明显降低（P〈0.05）,LVFS、LVEF显著升高（P〈0.05）。HE染色显示A、B两组心肌纤维化程度有所改善,并且两组改善情况相似。RT-PCR检测：与D组比较,A、B、C3组兔心肌组织ERK1/2 mRNA表达明显升高（P〈0.05）;治疗后,与C组比较,A组ERK1/2 mRNA表达均明显下调（P〈0.05）,B组ERK1 mRNA表达显著下调（P〈0.05）。与B组比较,A组ERK1/2 mRNA表达差异无统计学意义（P〉0.05）。与C组比较,A、B两组ERK1/2蛋白表达显著减少（P〈0.05）。结论：扶阳强心方能明显改善兔CHF兔血流动力学参数,其机制可能是通过调控CHF模型兔心肌组织内ERK1/2信号通路,影响ERK1/2信号通路的活化而改善血流动力学参数。

Objective： To explore the effects of Fuyang Qiangxin Decoction（ FQD） in the hemodynamic changes and ERK1/2 mRNA and protein expression in rabbit models of adriamycin-induced chronic heart failure（ CHF）. Methods：Forty New Zealand rabbits were randomly divided into four groups： FQD group（ A）,digoxin group（ B）,ear injection of adriamycin group（ C） and normal control group（ D）. Rabbits in the group A,B and C were used to establish models of adriamycin-induced avascular CHF,and group D received no treatment. Group A was fed with FQD（ 12 m L·kg^（-1）·d^（-1））. Group B was given digoxin（ 1. 25 μg·m L^（-1）·d^（-1）） orally. Group C and D were given the same amount of normal saline. After 30 days,the hemodynamic changes were measured by echocardiography. The morphological differences in the myocardial tissues were observed with hematoxylin-eosin（ HE） staining and ERK1/2 mRNA and protein expression were detected with RT-PCR and Western blot. Result： Compared with group C,LVDS and LVDD in group A and B were significantly lower and LVFS and LVEF increased significantly（ P 0. 05）. HE staining showed that A and B groups＇ myocardial fibrosis was improved. Compared with group D,rabbit myocardial tissue ERK1/2 mRNA expression was significantly increased in group A,B and C（ P 0. 05）. After treatment,compared with group C,ERK1/2 mRNA expression was significantly decreased in group A（ P 0. 05）,ERK1 mRNA expression was significantly lower in group B（ P 0. 05）. There was no significant difference between group A and B（ P 0. 05）. Compared with group C,ERK1/2 protein expression in the group A and B was significantly decreased（ P 0. 05）. Conclusion： FQD can significantly improve hemodynamic parameters of CHF rabbit model,which may suppress the activation ERK1/2 signal pathway through internal regulation of rabbit CHF myocardial tissue ERK1/2 signaling pathway.