参芪扶正注射液抑制ERK1/2、GATA4信号通路改善小鼠心力衰竭实验研究

目的:探讨参芪扶正注射液(SQ)治疗小鼠心力衰竭的疗效及机制。方法:将50只C57BL/6J小鼠随机分为正常组、模型组、阳性组、SQ低剂量组、SQ高剂量组,每组10只。异丙肾上腺素皮下注射诱导小鼠心力衰竭模型。SQ低剂量组和SQ高剂量组分别腹腔注射20、40 ml/kg参芪扶正注射液,阳性组给予80 mg/kg琥珀酸美托洛尔缓释片灌胃,正常组和模型组腹腔注射相应的0.9%氯化钠溶液。疗程14 d。观察治疗后小鼠左小室射血分数(LVEF)及左室短轴缩短率(LVFS),血清BNP浓度,心脏和肺脏脏器系数,心脏病理切片及心肌ERK1/2/GATA4信号通路的变化。结果:与正常组相比,模型组的LVEF和LVFS水平均有显著性降低,BNP浓度、心脏和肺脏脏器系数明显升高(P<0.05)。与模型组相比,阳性组、SQ低剂量组、SQ高剂量组的LVEF和LVFS水平均有显著性升高,BNP浓度、心脏和肺脏脏器系数明显下降(P<0.05),其中,SQ高剂量组LVEF、LVFS和BNP浓度改善优于SQ低剂量组(P<0.05)。病理切片显示,模型组心肌纤维化和炎症细胞浸润明显,阳性组、SQ低剂量组、SQ高剂量组心肌纤维大部分完整无炎症浸润。Western blot显示,模型组ERK1/2、p-ERK1/2、GATA4蛋白表达明显升高,阳性组、SQ低剂量组及SQ高剂量组ERK1/2、p-ERK1/2、GATA4蛋白表达明显减少(P<0.05)。结论:参芪扶正注射液可以改善心力衰竭小鼠的心脏收缩功能、减轻心肌纤维化,这种作用可能与抑制MAPK/ERK1/2/GATA4信号通路有关。

Effect of Shenqi Fuzheng injection on heart failure in mice by inhibiting ERK1/2,GATA4 signaling pathway

Objective:To investigate the therapeutic effect and mechanism of Shenqi Fuzheng injection(SQ)on heart failure in mice.Methods:Fifty C57BL/6J mice were randomly divided into normal group,model group,positive group,SQ low dose group and SQ high dose group,with 10 mice in each group.The heart failure model of mice was induced by subcutaneous injection of isoproterenol.The low-dose group and high-dose group were intraperitoneally injected with 20 ml/kg and 40 ml/kg Shenqi Fuzheng injection respectively.The positive group was intragastrically injected with 80 mg/kg metoprolol succinate sustained-release tablets.The normal group and model group were intraperitoneally injected with corresponding 0.9%normal saline.The course of treatment was 14 days.The changes of LVEF and LVFS,serum BNP concentration,heart and lung organ coefficient,cardiac pathological section and myocardial ERK1/2/GATA4 signaling pathway were observed after treatment.Results:Compared with the normal group,LVEF and LVFS levels of the model group were significantly decreased,BNP concentration,heart and lung organ coefficient were significantly increased(P<0.05).Compared with the model group,the levels of LVEF and LVFS in positive group,SQ low-dose group and SQ high-dose group were significantly increased,and the concentration of BNP,heart and lung organ coefficient were significantly decreased(P<0.05).The improvement of LVEF,LVFS and BNP in SQ high-dose group was better than that in SQ low-dose group(P<0.05).Pathological sections showed that myocardial fibrosis and inflammatory cell infiltration were obvious in the model group,and most of the myocardial fibers in the positive group,low-dose group and high-dose group were intact without inflammatory infiltration.Western blot showed that the protein expression of ERK1/2,p-ERK1/2 and GATA4 in the model group were significantly increased,while the protein expression of ERK1/2,p-ERK1/2 and GATA4 in the positive group,SQ low-dose group and SQ high-dose group was significantly decreased(P<0.05).Conclusion:Shenqi Fuzheng injection can improve cardiac systolic function and reduce myocardial fibrosis in mice with heart failure,which may be related to the inhibition of MAPK/ERK1/2/GATA4 signaling pathway.