真武胶囊联合苯那普利治疗扩张性心肌病实验研究

Effect of Zhenwu Capsule Combined with Benazepril on Dilated Cardiomyopathy in Rats

目的观察真武胶囊联合苯那普利治疗大鼠扩张性心肌病疗效。方法 32只2周龄Wistar雄性大鼠喂养呋喃唑酮8周,建立扩张性心肌病动物模型。造模成功后,随机等分为真武胶囊组、苯那普利组、联合组及模型对照组,每组8只,分别予灌胃真武胶囊[1.8g/(kg·d)]、苯那普利[3.33mg/(kg·d)]及真武胶囊联合苯那普利,模型对照组不干预,正常喂养。8周后超声测量大鼠左心室舒张末期内径(LVDD)、收缩末期内径(LVSD)、射血分数(LVEF);检测各组大鼠心肌胶原含量、心肌细胞凋亡指数,显微镜下观察心肌结构。结果 (1)大鼠左心室舒张末期内径(LVDD):真武胶囊组(0.57±0.05)cm,苯那普利组(0.56±0.10)cm,联合组(0.51±0.11)cm,均较模型对照组(0.67±0.03)cm明显缩小,差异有统计学意义(P<0.05);(2)大鼠左心室收缩末期内径(LVSD):真武胶囊组(0.34±0.12)cm,苯那普利组(0.35±0.06)cm,联合组(0.31±0.04)cm,均小于模型对照组的(0.42±0.01)cm,差异有统计学意义(P<0.05);(3)射血分数:真武胶囊组(59.3±2.1)%,苯那普利组(60.2±2.3)%,联合组(68.3±1.2)%,均高于模型对照组的(36.1±1.1)%,差异有统计学意义(P<0.05)。联合组LVDD、LVSD及射血分数均优于真武胶囊组与苯那普利组(P<0.05)。(4)大鼠心肌胶原含量:真武胶囊组(8.33±1.2)μg/mgprot,苯那普利组(8.22±2.1)μg/mgprot,联合组(6.34±1.1)μg/mgprot,均小于模型对照组的(10.45±2.2)μg/mgprot;(5)心肌细胞凋亡指数:真武胶囊组10.6±2.1,苯那普利组10.4±1.5,联合组8.2±1.4,均低于模型对照组的17.9±2.1,差异有统计学意义(P<0.05)。联合组较真武胶囊组和苯那普利组减少(P<0.05)。镜下观察,模型对照组大鼠心肌纤维排列紊乱,纤维结缔组织增生明显。联合组大鼠心肌纤维排列整齐,纤维结缔组织增生改善明显,优于真武胶囊组及苯那普利组。结论真武胶囊联合苯那普利能明显缩小大鼠扩大的心脏,提高射血分数,减少心肌胶原含量,抑制心肌细胞凋亡,改善心肌重构。

Objective To investigate the effect of Zhenwu capsule combined with benazepril on dilated cardiomyopathy（DCM） in rats. Methods Thirty-two male Wistar rats（2 weeks old） were fed with furazolidone for 8weeks to establish DCM model, then were randomly and equally divided into 4 groups： Zhenwu capsule group, benazepril group, Zhenwu capsule combined with benazepril group, and control group. Rats were given Zhenwu capsule [1.8g/（kg·d）], benazepril [3.33mg/（kg·d）] and Zhenwu capsule combined with benazepril by gavage in 3 treatment groups, respectively, while rats in control group were fed normally in absence of intervention. After 8 weeks,all rats were measured on left ventricular end-diastolic diameter（LVDD）, left ventricular end-systolic diameter（LVSD） and left ventricular ejection fraction（LVEF） by color doppler ultrasound, then were sacrificed to detect cardiac collagen contents, measure apoptosis index and observe the microstructure of myocardium by microscope.Results The LVDD was 0.57 ±0.05 cm in Zhenwu capsule group, 0.56 ±0.10 cm in benazepril group, and 0.51 ±0.11 cm in Zhenwu capsule combined with benazepril group, which were all higher than that in control group（0.67±0.03 cm, P〈0.05）. The LVSD was 0.34±0.12 cm, 0.35±0.06 cm, 0.31±0.04 cm in Zhenwu capsule group, benazepril group, and Zhenwu capsule combined with benazepril group, repectively, which were all lower than that in control group（0.42±0.01 cm, P〈0.05）. The LVEF was higher in 3 treatment groups than that in control group（59.3%±2.1%, 60.2%±2.3%, 68.3%±1.2% vs 36.1%±1.1%, P〈0.05）. The collagen content and myocardial apoptosis index were both lower in 3 treatment groups than that in control group（collagen： 8.33±1.20μg/mgprot, 8.22±2.1μg/mgprot,6.34 ±1.10μg/mgprot vs 10.45 ±2.2μg/mgprot; myocardial apoptosis index： 10.6 ±2.11, 10.4 ±1.5, 8.2 ±1.4 vs17.9 ±2.1;all P〈0.05）; a significant difference in myocardial apoptosis index was also found between combined drugs group and single drug groups（P〈0.05）. The cardiac fibrosis arranged in disorder and was significant proliferated in control group. Zhenwu capsule combined with benazepril improved the disorder and attenuated the proliferation of myocardial fibrosis, which was better than the effect in Zhenwu capsule and benazepri single drug groups. Conclusion Zhenwu capsule combined with benazepril can obviously reduce enlarged heart, enhance ejection fraction, lower collagen content, inhibit myocardial apoptosis, and improve myocardial remodeling.