摘要
目的:探究苦瓜总皂苷(MCS)通过神经调节蛋白 1(NRG-1)/红细胞白血病病毒癌基因同源物(ErbB)通路干预高血压心力衰竭(HF)大鼠心肌重构和纤维化的机制.方法:40只大鼠分为对照组、模型组、低剂量MCS组和高剂量MCS组(各10只).通过高盐饮食构建高血压HF模型.通过灌胃MCS进行干预(20 mg/kg和40mg/kg,6周).检测各组收缩压和心功能指标.HE染色、Masson染色和TUNEL染色分析MCS对高血压HF大鼠心肌损伤、纤维化和凋亡的影响.并比较各组心肌组织中NRG-1/ErbB通路mRNA和蛋白的表达量.结果:干预后,模型组的收缩压、LVEDP、Masson染色面积百分比(CVF)(7.94±0.82)％和凋亡指数(26.48±3.67)％显著高于对照组,而LVESP、±dp/dtmax、NRG-1和ErbB mRNA和蛋白水平显著低于对照组(P 均=0.001).低剂量 MCS 组和高剂量 MCS 组的收缩压、LVEDP、CVF[(5.26±0.51)％,(4.04±0.39)％]和凋亡指数[(17.35±2.01)％,(10.86±1.24)％]均显著低于模型组(P＜0.05或＜0.01),且高剂量MCS组的显著低于低剂量MCS组(P＜0.05或＜0.01).低剂量MCS组和高剂量MCS组的LVESP、±dp/dt max、NRG-1和ErbB mRNA和蛋白水平显著高于模型组(P＜0.05或＜0.01),且高剂量MCS组的显著高于低剂量MCS组(P＜0.05或＜0.01).结论:MCS可能通过剂量依赖性地诱导NRG-1/ErbB通路抑制心肌细胞凋亡和纤维化,从而延缓高血压HF进展.
Abstract
Objective:To explore the mechanism of momordica charantia saponins(MCS)intervening myocardial re-modeling and fibrosis in hypertensive rats with heart failure(HF)via neuregulins-1(NRG-1)/erythroblastic leukemia viral oncogene homolog(ErbB)pathway.Methods:The 40 rats were divided into control group,model group,low-dose MCS group and high-dose MCS group(n=10,respectively).A hypertensive HF model was con-structed through high salt diet.Intervention was performed by gavage of MCS(20 mg/kg and 40 mg/kg,6 weeks).Systolic blood pressure(SBP)and heart function indexes were detected in each group.HE staining,Masson staining and TUNEL staining were used to analyze the effects of MCS on myocardial injury,fibrosis and apoptosis in hyper-tensive HF rats.The expression levels of NRG-1/ErbB pathway mRNA and protein in myocardial tissues of each group were compared.Results:After intervention,SBP,LVEDP,Masson staining area percentage(CVF)(7.94± 0.82)％and apoptosis index(26.48±3.67)％of the model group were significantly higher than those of the control group,while LVESP,±dp/dt max,NRG-1 and ErbB mRNA and protein levels were significantly lower than those of the control group(P=0.001 all).SBP,LVEDP,CVF[(5.26±0.51)％,(4.04±0.39)％]and apoptosis index[(17.35±2.01)％,(10.86±1.24)％]of low-dose MCS group and high-dose MCS group were significantly lower than those of the model group(P＜0.05 or＜0.01),and those of high-dose MCS group were significantly lower than those of low-dose MCS group(P＜0.05 or＜0.01).LVESP,±dp/dtmax,NRG-1 and ErbB mRNA and protein levels in low-dose MCS group and high-dose MCS group were significantly higher than those of model group(P＜0.05 or＜0.01),and those of high-dose MCS group were significantly higher than those of low-dose MCS group(P＜0.05 or＜0.01).Conclusion:MCS may inhibit cardiomyocyte apoptosis and fibrosis through dose-dependent induction of NRG-1/ErbB pathway,thereby delaying progression of hypertensive HF.
维普
万方数据