坎地沙坦抑制慢性心衰大鼠心肌纤维化并降低心肌转化生长因子β1、结缔组织生长因子表达被引量：8

Inhibition of Candesartan on Myocardial Fibrosis and Attenuate Expression of TGF-β_1 and Connective Tissue Growth Factor in Rats with Chronic Heart Failure

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摘要目的探讨坎地沙坦改善慢性心衰大鼠心室重塑和抑制心肌纤维化(myocardial fibrosis,MF)可能的作用机制。方法采用肾上腹主动脉缩窄法制作的雄性Wistar大鼠慢性心衰模型,随机分为心衰组(HF组)及药物组(Drug组),另有假手术组(Sham组)作为对照。给药组大鼠予以坎地沙坦2mg·kg-1·d-1灌胃,HF组和Sham组用等体积生理盐水灌胃。4周后检测血流动力学参数,左室心肌胶原形态,左室质量指数(LVMI)、胶原容积分数(CVF)和血管周围胶原面积(PVCA),免疫组化法检测心室肌中转化生长因子(TGF-β1)、结缔组织生长因子(CTGF)表达。结果给药组大鼠与心衰组相比LVEDP降低,±dp/dtmax增高。LVMI,CVF,PVCA降低。TGF-β1,CTGF表达显著降低。结论坎地沙坦明显改善心室重塑、抑制MF,提高心功能。此作用可能与降低CTGF,TGF-β1表达有关。 OBJECTIVE To investigate the mechanism of candesartan to ameliorate ventricular remodeling and inhibit myocardial fibrosis（MF） in rats with chronic heart failure（CHF）. METHODS CHF Model was developed in male Wistar rats by suprarenal aortic constriction, then rats were randomly divided into two groups：HF group and candesartan group. Sham group were operated with the same method without aortic constriction. The rats in candesartan group were given a daily dose of 2 mg·kg^-1 of candesartan for 4 weeks by gastric gavage and the other two groups were fed with normal saline. Hemodynamic parameters of 3 groups were detecteded by multi-lead electric physiological instrument. The expressions of TGF-β1 and CTGF in myocardium were measured by qualitative and semiquantitative immunohistochemical staining. Masson staining was used in the study of total Collagen type in left ventricular interstitial tissue. Collagen volume fraction （CVF）, perivascular collagen area （PVCA） were measured by image analysis. RESULTS Compared with HF group,rats in candesartan group showed lower LVEDP and higher ＋dp/dtmax. The left ventrieular mass index（LVMI）, CVF, PVCA, and the expression of TGF-β1 and connective tissue growth factor （CTGF） in left ventricle decreased obviously. CONCLUSION Candesartan obviously ameliorates myocardial remodeling and inhibits MF of rats with CHF, improves cardiac function. The action mechanism is relative to the expressions of TGF-β1 and CTGF.

作者程劲松赵玉兰杨树涵柯元南

机构地区北京协和医学院研究生院北京中日友好医院郑州大学第二附属医院南阳医专第一附属医院

出处《中国药学杂志》 CAS CSCD 北大核心 2009年第11期832-835,共4页 Chinese Pharmaceutical Journal

基金河南省科技厅科研攻关项目(721023100230)

关键词慢性心力衰竭结缔组织生长因子坎地沙坦心肌纤维化转化生长因子Β1 chronic heart failure connective tissue growth factor candesartan myocardial fibrosis TGF-β1

分类号 R965 [医药卫生—药理学]

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