血管紧张素Ⅱ对肥厚心肌基质金属蛋白酶及细胞外基质的影响

目的: 探讨血管紧张素Ⅱ(AngⅡ)受体（AT₁,AT₂）拮抗剂对梗死心脏肥厚心肌组织基质金属蛋白酶(MMPs)及细胞外基质成份的影响。方法: 结扎大鼠左冠状动脉建立心肌梗死模型，术前7 d起分别用安慰剂、AT₁受体拮抗剂撷沙坦（valsartan）（10 mg·kg^-1·d^-1）、AT₂受体拮抗剂PD123319（30 mg·kg^-1·d^-1）。术后1、3、7、14 d分别检测室间隔（IS）MMP-2,3,9及其抑制物-1（TIMP-1）蛋白表达，以及细胞基质纤连蛋白（FN）、肌腱蛋白（TN-C）表达，免疫荧光分析FN、TN-C分布。结果: 心肌梗死14 d, IS呈典型的肥厚心肌病变。 手术组大鼠室间隔MMP-2、3、9及TN-C蛋白表达显著高于假手术组（P<0.01），TIMP-1和FN蛋白表达显著降低（P<0.01）; 手术加valsartan组 MMP-2、3、9 和 TN-C 蛋白表达明显低于手术组及手术加PD123319组, 相反， TIMP-1 和FN 蛋白表达显著高于手术组及手术加PD123319组 (P<0.01); 手术组与手术加PD123319组间MMP-2、3、9、TIMP-1、FN、TN-C蛋白表达差异无显著（P>0.05）。结论: AngⅡ参与心肌梗死心肌组织的重塑，通过AT1起作用调节MMPs降解细胞外基质， AT₁受体拮抗剂的心脏保护作用与其抑制MMPs有关。

Effects of angiotension Ⅱ on metalloproteinases and matrix in hypertrophied myocardium from infarcted rats

AIM: To investigate the roles of angiotensionⅡ (AngⅡ) receptors (AT₁, AT₂) antagonists on matrix metalloproteinases (MMPs) and extracellular matrix (ECM) system in septal myocardium from infarcted rats.METHODS: The model of rat myocardium infarction (MI) was established by permanent ligation of the left coronary artery. The treatments of the AT₁ receptor antagonist valsartan (10 mg·kg^-1·d^-1) or AT₂ receptor antagonist PD123319 (30 mg·kg^-1·d^-1) were started 7 days prior to surgery. On day 14 after MI, protein levels of MMP-2, 3, 9, fibronectin (FN), tenascin-C (TN-C) in interventricular septum (IS) were determined. The distributions of FN and TN-C were also determined by immunofluorescence.RESULTS: Pathological changes of IS on day 14 after MI showed typical myocardial hypertrophy. Protein expressions of MMP-2, 3, 9 and TN-C of IS in banding group were higher than those in sham-operation group (P<0.01). The expressions of TIMP-1 and FN were lower than those in sham-operation group (P<0.01). Protein expressions of MMP-2, 3, 9 and TN-C in valsartan group were obviously lower than those in banding and PD123319 groups (P<0.01). TIMP-1 and FN protein expressions in valsartan group were higher than those in banding and PD123319 groups (P<0.01). No difference between banding and PD123319 groups was observed (P>0.05).CONCLUSION: AngⅡis involved in myocardium remodeling in infarcted rats, which is mediated via AT₁ receptor to degrade matrix by MMPs. The heart protection of AT₁ receptor antagonists may relate to inhibition of MMPs.