缬沙坦对腹主动脉缩窄大鼠心肌及冠状动脉重塑的影响

EFFECTS OF VALSARTAN ON MYOCARDIAL AND CORONARY ARTERIAL REMODELING IN ABDOMINAL AORTA CONSTRICTED RATS

目的观察血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)Ⅰ型(AT1)受体拮抗剂缬沙坦对腹主动脉缩窄(AC)大鼠心肌与冠状动脉重塑的影响,并探讨其可能的机制。方法将腹主动脉缩窄术后SD大鼠随机分为:AC对照组;AC+低剂量缬沙坦(1mg/kg/d)组;AC+高剂量缬沙坦(30mg/kg/d)组,每组8只。另设假手术组8只作为正常对照。假手术组及AC对照组给予安慰剂灌胃。治疗6周后,检测各组大鼠颈动脉压、左室重量指数(leftventricularmassindex,LVMI)。vanGieson染色检测心肌胶原容积分数(collagenvolumefraction,CVF)及冠状动脉壁厚度/内径比值。放射免疫法检测血浆及心肌中AngⅡ浓度。免疫组化法检测心脏结缔组织生长因子(connectivetissuegrowthfactor,CT-GF)的表达。结果AC对照组大鼠颈动脉压、LVMI、CVF、冠状动脉中层/内径比值以及CTGF表达均显著高于假手术组(P<0·01)。与AC对照组相比,上述所有指标在高剂量缬沙坦组均明显下降(P<0·01)。低剂量缬沙坦组颈动脉压与AC对照组相比无显著性差异(P>0·05),但上述其他指标则明显低于AC对照组(P<0·05或P<0·01)。结论缬沙坦能有效抑制腹主动脉缩窄大鼠的心肌及冠状动脉重塑。其可能机制是阻滞了心肌局部的AT1受体,并下调CTGF的表达。

Objective To investigate the effects of valsartan on myocardial remodeling and coronary arterial angiotension Ⅱ typel （AT1） receptor antagonist remodeling in abdominal aorta constricted （AC） rats, and to explore the mechanism. Methods Five days after suprarenal abdominal aorta constriction, 24 male SD rats were randomly divided into three groups： AC control group; AC＋low dose valsartan （1mg/ kg/d） treatment group and AC＋high dose valsartan （30mg/kg/d） treatment group of 8 rats each. Eight sham-operated rats served as controls. After 6 weeks of therapy, the rats were sacrificed. The body weight, carotid pressure, and LVMI were recorded. The sections of the hearts were stained with van Gieson staining to examine CVF and the ratio of coronary arterial media thickness/diameter of lumen. The concentration of Ang Ⅱ in plasma and myocardial tissue was determined with radioimmunoassay. The expression of connective tissue growth factor in cardic myocytes was assessed by immunohistochemistry. Results Compared with those in sham-operated rats, the carotid pressure, LVMI, CVF, coronary arterial media/diameter of lumen ratio and CTGF expression in the hearts were significantly increased in the AC control group （all P〈0.01）. Compared with those of the AC control group, all the parameters were significantly decreased in the high-dose valsartan treatment group. There was no significant difference in carotid pressure between the AC control group and the low-dose valsartan treatment group （P〉0.05）, but other parameters in the latter were significantly reduced compared with those of the former （P〈0.05 or P〈0.01）. Conclusion Valsartan is effective in suppressing myocardial and coronary arterial remodeling. The proposed mechanism of this protective effect is the blockade of AT1 receptors and the down-regulation of CTGF expression.