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- 2017
泻肺利水中药对心力衰竭大鼠左室重构的影响
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Abstract:
摘要：目的 观察泻肺利水中药对心力衰竭大鼠左室重构的影响。方法 阿霉素腹腔注射建立大鼠心力衰竭模型，随机分为模型组、中药组、卡托普利组和地高辛组，分别以蒸馏水、泻肺利水中药[22g/(kg？d)]、卡托普利？？[19mg/(kg？d)]？？和地高辛[32μg/(kg？d)]连续灌胃35d，并另设假手术组，观察大鼠心功能和左室重构指标，ELISA法检测血浆脑钠肽、肾素、血管紧张素Ⅱ和醛固酮水平，TUNEL法检测心肌细胞凋亡并计算凋亡指数，Masson染色观察心肌胶原情况并计算心肌胶原容积分数，RT-PCR检测心脏基质金属蛋白酶2(MMP-2)、9(MMP-9)及其组织抑制因子1(TIMP-1)、2(TIMP-2)的基因表达水平。结果 与假手术组比较，模型组大鼠心功能下降并出现左室重构，血浆脑钠肽、肾素、血管紧张素Ⅱ和醛固酮水平、心肌细胞凋亡指数和胶原容积分数显著升高，心肌MMP-2/9和TIMP-1/2的基因表达显著上调(P<0.01或P<0.05)。与模型组比较，中药组、卡托普利组和地高辛组大鼠心功能显著升高，左室重构显著减轻，血浆脑钠肽和醛固酮水平、心肌细胞凋亡指数显著降低(P<0.01或P<0.05)；中药组和卡托普利组血浆血管紧张素Ⅱ水平和胶原容积分数显著降低(P<0.01或P<0.05)；中药组心肌MMP-2/9、TIMP-1/2的基因表达显著下调(P<0.01或P<0.05)；卡托普利组心肌MMP-9和TIMP-2的基因表达显著下调(P<0.01或P<0.05)。结论 泻肺利水中药可以减轻心力衰竭大鼠左室重构，改善心功能，机制可能与降低心肌MMP-2、MMP-9、TIMP-1和TIMP-2的基因表达水平，抑制心肌细胞凋亡、减轻心肌纤维化有关。
ABSTRACT: Objective To investigate the effects of Xiefei Lishui recipe on left ventricle remodeling in rats with heart failure. Methods Heart failure rat model was induced by intraperitoneal injections of doxorubicin. Rats were randomly divided into sham operation group (sham group), model group, traditional Chinese medicine group (TCM group), captopril group, and digoxin group. Distilled water, TCM [22g/(kg？d)], captopril [19mg/(kg？d)], and digoxin [32μg/(kg？d)] were administered by gastrogavage in rats in different groups for 35 days, respectively. Indices of ventricle remodeling and cardiac function, plasma levels of B-type natriuretic peptide (BNP), rennin (REN), angiotensin Ⅱ(AngⅡ) and aldosterone (ALD) were measured. Cardiomyocyte apoptosis index and collagen volume fraction (CVF) were analyzed. We also assayed myocardial mRNA expressions of MMP-2/9 and TIMP-1/2, and their tissue inhibiting factors TIMP-1 and TIMP-2. Results Compared with those in sham group, in model group cardiac function was significantly decreased, which could be significantly increased by TCM or captopril or digoxin, indices of cardiac remodeling were significantly increased, which could be significantly decreased by TCM or captopril (P<0.01 or P<0.05). Plasma levels of BNP, REN, AngⅡ and ALD, cardiomyocyte apoptosis index and CVF in model group were significantly increased, could be significantly decreased by TCM or captopril (P<0.01 or P<0.05). Myocardial mRNA expressions of MMP-2, MMP-9, TIMP-1 and TIMP-2 in model group were significantly upregulated compared with those in sham group, which could be significantly downregulated by TCM (P<0.01 or P<0.05). Conclusion Xiefei Lishui recipe can attenuate left ventricle remodeling and improve cardiac function in rats with heart failure, which may be
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