芪苈强心胶囊联合沙库巴曲缬沙坦对心力衰竭大鼠的作用研究

Effect of Qili Qiangxin Capsule combined with sacubitril valsartan sodium tablet in rats with heart failure

关键词:  心力衰竭  芪苈强心胶囊  沙库巴曲缬沙坦  阿霉素

Key words:  heart failure  Qili Qiangxin Capsule  sacubitril valsartan sodium tablet  doxorubicin

摘要:

[目的] 观察芪苈强心胶囊（QLQX）联合沙库巴曲缬沙坦（LCZ696）对心力衰竭大鼠模型的作用。[方法] 选取40只成年雄性SD大鼠，随机选取8只作为对照组，其余 32 只大鼠利用阿霉素腹腔注射6周建立心力衰竭模型，对照组腹腔注射等量生理盐水。多普勒超声评估动物模型建立成功后，将32只大鼠随机分为 QLQX 联合 LCZ696 组、QLQX 组、LCZ696 组及模型组，每组 8 只，灌胃 4 周。于给药前及给药结束后通过多普勒超声评估各组大鼠的心脏结构及功能，获得经胸二维 M 型超声心动图，并检测射血分数（LVEF）、短轴缩短率（LVFS）、左心室舒张末期内径（LVEDD）、左心室收缩末期内径（LVESD）、左室舒张末期后壁厚度（LVPWD）、舒张期室间隔厚度（IVSD）、左心室收缩末期容积（LVESV）等参数；苏木精-伊红（HE）染色观察心肌组织形态学变化情况；Masson 3 色染色观察各组心肌纤维化情况；酶联免疫吸附法（ELISA）测定 N-端脑钠肽前体（NT-proBNP）、肾素-血管紧张素-醛固酮系统（RAAS 系统）指标、炎性因子水平。[结果] 与模型组比较，3 个治疗组均能一定程度上减轻心力衰竭大鼠乏力、纳差、便溏、水肿等表现，QLQX 联合 LCZ696 组大鼠效果最好；3 个治疗组大鼠全心质量指数均有明显好转（P＜0.05），组间比较无明显差异（P>0.05）；LVEF、LVFS 明显升高（P＜0.05），LVEDD、LVESD、LVESV、LVPWD、IVSD 显著降低（P＜0.05）；与 QLQX组和 LCZ696 组比较，QLQX 联合 LCZ696 组 LVEF、LVFS 明显升高（P＜0.01），LVEDD、LVESD、LVESV、LVPWD 显著降低（P＜0.05）；3 个治疗组间 IVSD 未见明显差异（P>0.05）；与模型组比较，3 个治疗组 NT-proBNP、RAAS 系统指标及炎性因子水平显著降低（P＜0.05）；心肌细胞损伤程度明显减轻、心肌纤维化程度明显好转（P＜0.05）；QLQX联合LCZ696组的效果优于其他两组（P＜0.05）。[结论] QLQX 联合LCZ696能有效改善心力衰竭大鼠一般状态，改善心室重构及心肌重塑；能有效抑制 RAAS 系统、降低炎性因子水平，且较单用QLQX或LCZ696更高效。

Abstract:

[Objective] To observe the effect of Qili Qiangxin Capsule （QLQX） combined with sacubitril valsartan sodium tablets （LCZ696） on the rat model of heart failure. [Methods] Selecting forty adult male SD rats，eight rats were randomly selected individuals as the control group，the remaining 32 rats developed a heart failure model by intraperitoneal injection for 6 weeks，the control group received an intraperitoneal injection of an equivalent amount of normal saline. After successfully establishmenting the animal model， 32 rats were randomly divided into QLQX combined with LCZ696，QLQX，LCZ696 and model groups，8 animals in each group，Gavage for 4 weeks. The cardiac structure and function of the rats were evaluated by colour Doppler echocardiography before and after the administration，obtained transthoracic 2D M echocardiography，and detect ejection fraction （LVEF），short axis shortening rate（LVFS），left ventricular end diastolic diameter（LVEDD），left ventricular end systolic diameter（LVESD），left ventricular posterior end diastolic wall thickness （LVPWD），diastolic ventricular septal thickness （IVSD），left ventricular end systolic volume （LVESV） and other parameters；cardiac histomorphological changes were observed by HE staining；Masson Cardiac fibrosis in each group was observed by trichrome staining；enzyme-linked immunoassay is used to determine the levels of N-encephalic natriuretic peptide precursor （NT-proBNP），the index of RAAS system and inflammatory factors. [Results] Compared with the model group，all three treatment groups could reduce the fatigue，poor appetite，loose stool，edema in rats with heart failure to some extent，however，the QLQX combined with the LCZ696 group of rats had the best effect；the whole heart mass index of rats in the three treatment groups improved obviously （P＜0.05）， however，there was no significant difference between the three groups（P>0.05）；LVEF and LVFS were significantly increased（P＜0.05）， and LVEDD，LVESD，LVESV，LVPWD，and IVSD were all significantly decreased（P＜0.05）；compared with QLQX group and the LCZ696 group，LVEF and LVFS were increased significantly in QLQX combined with LCZ696 group（P＜0.01），and LVEDD，LVESD， LVESV，and LVPWD were significantly decreased（P＜0.05）；no significant difference in IVSD between the three treatment groups（P> 0.05）；compared with the model group，the levels of NT-proBNP，RAAS system indicators and inflammatory factors were significantly reduced in the three treatment groups （P＜0.05），the degree of cardiomyocyte injury was significantly reduced，and the degree of myocardial fibrosis was significantly improved（P＜0.05）；QLQX and LCZ696 group performed better than the other two groups（P＜0.05）. [Conclusion] QLQX combined with LCZ696 can effectively improve the general state of heart failure rats，improve ventricular remodeling and myocardial remodeling. It can effectively inhibit the RAAS system and reduce the level of inflammatory factors，and is more efficient than QLQX or LCZ696 alone.