黄芪保心汤对阿霉素诱导扩张型心肌病大鼠心室重构的影响

目的?初步探讨黄芪保心汤对阿霉素诱导扩张型心肌病大鼠心室重构的影响及机制。方法?90只SD大鼠腹腔注射阿霉素建立DCM模型，成模55只，随机分组给药如下:模型组（等体积生理盐水）、黄芪保心汤低、中、高剂量组（分别予合生药量5.67、11.34、22.68?g/kg），卡托普利组（6.75?mg/kg），每组11只，每日喂药1次。另设正常对照组大鼠10只（等体积生理盐水）。4周后，超声心动图检测左室结构及功能变化；颈动脉插管检测血流动力学指标；观察心肌组织形态学改变；ELISA法检测血清N末端脑钠肽前体（NT-proBNP）、基质裂解素2（ST2）、血管紧张素Ⅱ（AngⅡ）、醛固酮（ALD）、肾素活性（Renin）；比色法测定心肌细胞超氧化物歧化酶（SOD）活性，脂质过氧化物丙二醛（MDA）和乳酸脱氢酶（LDH）含量。结果?与正常组比较，模型组大鼠LVEDD、LVESD增高，EF、FS降低（P<0.01）；LVDP、±dp/dtmax减低，LVEDP升高（P<0.01）；心脏质量指数增大（P<0.01）；心肌细胞排列紊乱，大量纤维组织增生；血NT-proBNP、ST2、Renin、AngⅡ、ALD水平均升高（P<0.01）；SOD水平降低，MDA、LDH升高（P<0.01）。与模型组比较，黄芪保心汤低、中、高剂量组可不同程度地降低大鼠LVEDD、LVESD，升高EF、FS值（P<0.05~0.01）；升高LVDP、±dp/dtmax，降低LVEDP（P<0.05~0.01）；降低HWI和LVMI（P<0.05~0.01）；心肌细胞排列整齐，纤维组织增生减轻；血NT-proBNP、ST2、Renin、AngⅡ、ALD水平不同程度下降（P<0.05~0.01）；降低MDA和LDH，并升高SOD水平（P<0.05~0.01）。各剂量组对上述指标的改善程度呈一定的剂量-效应关系。结论?黄芪保心汤可改善扩张型心肌病大鼠心脏肥大、纤维化增生，通过调控氧化因子、抑制RAAS神经内分泌因子激活，改善心功能，抑制心室重构。 

Effect of Huangqi Baoxin Decoction on Ventricular Remodeling in Rats with Dilated Cardiomyopathy Induced by Adriamycin

OBJECTIVE?To preliminary discuss the influence and mechanism of Huangqi Baoxin Decoction on ventricular remodeling in rats with dilated cardiomyopathy (DCM) induced by adriamycin. METHODS?90 SD rats were given intraperitoneal injection of adriamycin to establish the DCM model， with 55 rats model being succeed. Then they were randomly divided into model group (the same volume of physiological saline solution)， low-dose group with Huangqibaoxin Decoction (5.67 g/kg)， middle-dose group with Huangqibaoxin Decoction (11.34 g/kg)， high-dose group with Huangqibaoxin Decoction (22.68 g/kg)， and captopril group (6.75 mg/kg of captopril)， with 11 rats in each group. The rats were given orally administrated drugs once a day， with 10 rats in the normal control group being treated with the same volume of physiological saline solution. 4 weeks later， rats in each group went through the echocardiography to access the construction and function of their left ventricular. Crotid artery intubation was applied to monitor their hemodynamic indexes， with changes of myocardial tissue morphology being observed. Besides， NT-proBNP， ST2， AngⅡ， ALD and Renin were tested through ELISA， together with the activity of SOD， MDA， and LDH being tested via colorimetric method. RESULTS?Compared with the normal group， the LVEDD and LVESD in rats of the model group were increased， with EF and FS being decreased (P<0.01). The LVDP，±dp/dtmax went down， while the LVEDP went up(P<0.01).The heart weight index increased(P<0.01)， with the myocardial cells being arranged in disorder and massive hyperplasia of fibrous tissue. The NT-proBNP， ST2， Renin， AngⅡ and ALD level increased(P<0.01). The level of SOD decreased， while the content of LDH and MDA increased (P<0.01). Compared to the model group， LVEDD and LVESD levels in the low， middle and high dose group of Huangqi Baoxin Decoction were reduced to varying degrees， with increased EF and FS (P<0.05~0.01). They experienced an increased LVDP，±dp/dtmax and decreased LVEDP(P<0.05~0.01)， decreased HWI and LVMI(P<0.05~0.01). And the myocardial cells were neatly arranged， the hyperplasia of fibrous tissue were relived. Besides， the levels of NT-proBNP， ST2， Renin， AngⅡ and ALD went down on diverse degree(P<0.05~0.01)， with decreased LDH and MDA and increased SOD(P<0.05~0.01). There was a dose-effect relationship among the groups of different doses towards the improvement on the above indexes. CONCLUSION?Huangqi Baoxin Decoction can improve the cardiac hypertrophy and fibrosis in rats with dilated cardiomyopathy. It also improves the cardiac function and inhibits ventricular remodeling by regulating the oxidation factors and inhibiting the activation of RAAS neuroendocrine factors.