摘要
目的比较单独使用氯沙坦或辛伐他汀和联合投药对逆转压力负荷心力衰竭大鼠心室肌纤维化的作用。方法使用降主动脉缩窄术建立大鼠压力负荷心衰模型。大鼠随机分为6组(n=8～10):正常对照组、假手术组、模型组、氯沙坦组、辛伐他汀组及联合投药组。5wk时比较各组大鼠心脏重量,计算重量指数;Masson染色观察心肌胶原组织增生;ELISA法检测血BNP浓度;RT-PCR法检测心室Collagen-Ⅰ和Collagen-ⅢmRNA表达,计算两者比例。结果与空白对照组和假手术组比较,DAC组心脏重量及其指数、左心重量及其指数和BNP水平均明显升高(P<0.01),Collagen-Ⅰ和Collagen-ⅢmRNA及两者比例均明显增加(P<0.05);投药组与DAC组比较,上述各指标均明显降低(P<0.05),联合投药效果更明显(P<0.05)。结论氯沙坦和辛伐他汀可缓解心衰时心室心肌纤维化,联合投药效果更明显,可能与降低Ⅰ型和Ⅲ型胶原含量及其比例有关。
Aim To nation of simvastatin investigate the effect of the combiand losartan on myocardial fibrosis after pressure overload state in rats. Methods The heart failure model was constriction （ DAC ）. 120 induced by descending aortic SD rats were randomized into 6 groups： normal control group, control sham group, model group,losartan group, simvastatin group, combination of losartan and simvastatin group. After drug treatment for 35 days, hearts were excised and weighed, the serum BNP level was measured by ELISA, mRNA levels of Collagen- Ⅰ and Collagen-Ⅲ were measured by RT-PCR, and Collagen- Ⅰ mRNA/ Collagen-Ⅲ mRNA ratio was calculated as well. Collagen was quantified by Masson staining. Results Histological analysis revealed myocardial fibrosis in left ventrieular sections. HW/BW ratio and LV Weight/LV weight ratio in DAC rats, as well as the BNP all in-creased significantly （ all, P 〈 0.01 ） , which were inhibited by drug treatment （ all, P 〈 0. 05 ）. Especially combination of two drugs （ P 〈 0.05 ）. RT-PCR showed that Collagen-Ⅰ and Collagen-Ⅲ expressions, as well as Collagen-Ⅰ mRNA/Collagen-Ⅲ mRNA ratio increased significantly （ all, P 〈 0. 05 ） in DAC rats and drug treatment downregulated them significantly （ all, P 〈0. 05 ）. Combination of two drugs showed more reduction than single drug treatment significantly （P 〈 0. 05）. Conclusions These findings indicate that the combination of simvastatin and losartan can attenuate the development of left ventricular myocardial fibrosis after pressure overload state more than the single drug treatment.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2009年第10期1376-1379,共4页
Chinese Pharmacological Bulletin
关键词
辛伐他汀
氯沙坦
心力衰竭
心肌纤维化
胶原重构
大鼠
simvastatin
losartan
heart failure
myocar
dial fibrosis
collagen remodeling
rats
