益心泰丸对阿霉素致心力衰竭大鼠心肌细胞凋亡的影响及作用机制  

Effect of Yixintai Pill on cardiomyocyte apoptosis in rats with cardiac failure caused by adriamycin and its mechanism

作　　者：孙涛[1] 郭志华(指导)[2] 曾英[3] SUN Tao;GUO Zhi-Hua;ZENG Ying(Department of Cardiology,the First Affiliated Hospital of Hunan University of Chinese Medicine,Changsha 410000,China)

机构地区：[1]湖南中医药大学第一附属医院心血管科,长沙410000 [2]湖南中医药大学,长沙410000 [3]湖南中医药大学第一附属医院心内科,长沙410000

出　　处：《中国免疫学杂志》2020年第21期2592-2596,共5页Chinese Journal of Immunology

基　　金：湖南省中医药管理局课题(201833)。

摘　　要：目的:探讨益心泰丸保护阿霉素(ADR)致心力衰竭(HF)大鼠心肌细胞凋亡的影响及作用机制。方法:将60只健康雄性Wistar大鼠随机分为4组,空白对照组、模型组、开博通组、益心泰丸组,腹腔一次性注射阿霉素(2.5 mg/kg)构建HF大鼠模型,对照组灌胃给予等体积生理盐水,益心泰丸组和开博通组分别灌胃给予相应药物5 mg/kg,用药4周。停药后空腹采血检测PRA、AngⅡ、ALD的含量,B超检测心脏结构,计算心体比,HE染色观察大鼠心肌组织病变,TUNEL法观察心肌细胞凋亡,ELISA法检测血清TNF-α和IL-6的表达,Western blot检测心肌组织中Akt、p-Akt、GSK-3β、P-GSK-3β蛋白的表达。结果:模型组PRA、AngⅡ、ALD、LVPWs、LVPWd、IVSs、IVSd、心脏/体重(HW/BW)、TNF-α、IL-6水平显著高于空白对照组,差异具有统计学意义(P<0.05)。益心泰丸组和开博通组PRA、AngⅡ、ALD、LVPWs、LVPWd、IVSs、IVSd、心脏/体重(HW/BW)、TNF-α、IL-6水平显著低于模型组,差异具有统计学意义(P<0.05);益心泰丸组、开博通组相比,差异无统计学意义(P>0.05)。模型组大鼠心肌呈片状坏死、空泡性变性、心肌纤维增多、心肌细胞片状溶解;空白对照组大鼠心肌细胞排列整齐、少量成纤维细胞、心肌细胞结构清晰;益心泰丸组和开博通组心肌纤维化、变性等较轻,肌纤维变性、纤维组织增生明显减少;与空白对照组相比,模型组AI数值明显升高,益心泰丸组、开博通组与模型组相比AI数值均明显下降,差异均具有统计学意义(P<0.05);与空白对照组相比,模型组p-Akt、p-GSK-3β水平明显下降,益心泰丸组和开博通组的p-Akt、p-GSK-3β显著高于模型组,差异具有统计学意义(P<0.05),益心泰丸组与开博通组相比,差异无统计学意义(P>0.05)。结论:益心泰丸可能通过上调PI3K/Akt/GSK-3β信号通路,抑制细胞凋亡,抑制心室重构,从而保护心脏功能。Objective:To investigate the effect and mechanism of Yixintai Pill on cardiomyocyte apoptosis induced by adriamycin(ADR)in rats with heart failure(HF).Methods:60 healthy male Wistar rats were randomly divided into four groups:blank control group,model group,captopril group and Yixintai Pill group.HF rat models were established by intraperitoneal injection of adriamycin(2.5 mg/kg).The control group was given the same volume of normal saline,and Yixintai Pill group and captopril group were given the corresponding drugs 5 mg/kg for 4 weeks.The contents of PRA,AngⅡand ALD were detected by fasting blood collection after drug with drawal,the cardiac structure was detected by B ultrasound,the heart-body ratio was calculated,the pathological changes of rat myocardial tissue were observed by HE staining,myocardial cell apoptosis was observed by TUNEL method,the expressions of serum TNF-αand IL-6 were detected by ELISA method,and the expressions of Akt,p-Akt,GSK-3βand P-GSK-3βproteins in myocardial tissue were detected by Western blot.Results:Levels of PRA,AngⅡ,ALD,LVPWs,LVPWd,IVSs,IVSd,heart/body weight(HW/BW),TNF-α,IL-6 in model group were significantly higher than those in control group,and the difference was statistically significant(P<0.05).Levels of PRA,AngⅡ,ALD,LVPWs,LVPWd,IVSs,IVSd,heart/body weight(HW/BW),TNF-α,IL-6 in Yixintai Pill group and captopril group were significantly lower than those in model group,and the difference was statistically significant(P<0.05).There was no significant difference between Yixintai Pill group and captopril group(P>0.05).In the model group,the myocardium showed lamellar necrosis,vacuolar degeneration,myocardial fibrosis and lamellar lysis of myocardial cells.In the control group,the myocardial cells were arranged orderly,a small number of fibroblasts,and the myocardial cell structure was clear.The myocardial fibrosis and degeneration in Yixintai Pill group and captopril group were lighter,and the muscle fibrosis and fibrous tissue hyperplasia were significantly reduced.

关 键 词：益心泰丸 开博通 心肌病 心肌细胞凋亡 心脏功能 

分 类 号：R392.5[医药卫生—免疫学]