摘要
目的探讨压力负荷下心肌组织基质金属蛋白酶家族(MMPs)MMP-2、3、9与其抑制物-1(TIMP-1)的变化,及血管紧张素受体拮抗剂对MMP-2、3、9、TIMP-1及细胞外基质纤连蛋白(fibronectin,FN)的影响。方法腹主动脉缩窄法建立大鼠超压力负荷模型,实验动物分为手术组(n=8);缬沙坦(val-sartan)组(n=8):手术组+缬沙坦(1 mg/kg.d);PD123319组(n=8):手术+PD123319(30 mg/kg.d)组;假手术组(n=8)。免疫沉淀法检测心肌组织MMP-2、3、9及TIMP-1,免疫荧光检测FN分布。结果大鼠术后14 d,缬沙坦组血浆AngⅡ浓度显著高于假手术组及PD123319组(P<0.05),缬沙坦组心肌AngⅡ浓度则低于假手术组及PD123319组(P<0.05)。手术组MMP-2、3、9蛋白表达显著高于假手术组(P<0.01),手术组TIMP-1、FN蛋白表达显著低于假手术组(P<0.01);缬沙坦组MMP-2、3、9显著低于手术组及PD123319组(P<0.05),缬沙坦组TIMP-1、FN显著高于手术组及PD123319组(P<0.05)。MMP-2、3、9、TIMP-1及FN蛋白表达在手术组与PD123319组间差异没有显著性(P>0.05)。结论超压力负荷下,心肌组织MMP-2、3、9表达量的增高,细胞外基质FN,参与心肌重构的病理过程,主要通过AT1起作用。
Objective To invesitgate the effect of matrix metalloproteinase-2, 3, 9（MMP-2,3,9） and tissue inhibitor of matrix metalloproteinase-1（TIMP-1） in hyptertrophied myoeardium induced by overloaded pressure in rats, and the effect of angiotension Ⅱ （Ang Ⅱ） receptors （AT1, AT2） antagonists on MMPs, TIMP-1 and fibronectin（FN）. Methods Pressure overloaded rat model was established by abdominal or banding operation. Thirty male wistar rats were divided randomly into four groups： shamoperated group, banding group, valsartan group, and PD123319（antagonist of AT2 receptor） group. AngⅡ concentration in serum and left ventricular myocardium were measured by radioimmunoassays. Protein expressions of MMP-2,3,9 and TIMP-1 were determined by immunoprecitipation, FN distribution was determined by immunoflorescence. Results In handing group, Aug Ⅱ concentration in serum and left ventricular myocardium tissue was higher than that in of sham-operated group, valsartan group and PD123319 group（P〈0.01） ; which was associated with higher protein expressions of MMP-2, 3, 9 in myocardium and lower the expression of TIMP-1 and FN （P〈0.01 ）. Valsartan significantly decreases protein expression of MMP-2, 3, 9 （P〈0.05） and increases TIMP-1, FN protein expression（P〈0.05）. Conclusion MMPs, TIMP-1 are involved in myocardium remodeling in pressure overloaded rat model. AT1 receptor antagonists decreased, MMPs and FN increased.
出处
《高血压杂志》
CSCD
北大核心
2006年第4期290-294,共5页
Chinese Journal of Hypertension
