高血压大鼠心肌中MMP-2的蛋白表达及其RAS阻断后的变化

Protein Expression of Matrix Metalloproteinase-2 in Heart of Hypertensive Rats and Its Changes After Blockage of RAS

[目的]探讨高血压大鼠左室心肌中基质金属蛋白酶-2(MMP-2)蛋白表达的变化以及血管紧张素转化酶抑制剂(ACEI)、血管紧张素Ⅱ1型受体拮抗剂(AT1-ant)单独与联合治疗对高血压大鼠心肌中MMP-2蛋白表达的影响。[方法]40只雄性8周龄的易卒中自发性高血压大鼠(SHRSP)随机分成5组:SHRSP对照组、安慰剂组、缬沙坦组、苯那普利组及缬沙坦与苯那普利联用组。另外,取8只雄性8周龄的京都Wistar大鼠(WKY)作为对照。利用免疫组织化学的方法检测WKY以及SHRSP左室心肌中MMP-2蛋白的表达。[结果]SHRSP的收缩压(SBP)、左室质量指数(LVMI)、胶原容积分数(CVF)、血管周围胶原面积(PVCA)、左室心肌MMP-2蛋白表达较同龄的WKY显著增高。给予苯那普利、缬沙坦单独或联合治疗后SHRSP的LVMI、CVF、PVCA、左室心肌 MMP-2蛋白表达都显著降低。苯那普利、缬沙坦单独应用时的效果没有差异,而联合应用的效果更显著。[结论]SHRSP左室心肌中MMP-2蛋白表达增高,肾素血管紧张素系统(RAS)阻断后MMP-2蛋白表达显著减少;苯那普利、缬沙坦逆转高血压心室重塑的作用可能部分通过下调MMP-2蛋白表达而实现;苯那普利和缬沙坦都能降低SHRSP的血压以及逆转其左室重塑,而联合用药的作用更显著。

[Objective] To observe matrix metalloproteinase-2 (MMP-2) protein expression in the left ventricular myocardium of stroke-prone spontaneously hypertensive rats (SHRSP) , and to evaluate the effects of combination of ACEI and ATI-ant as wall as the effects of either agent alone on MMP-2 protein expression. [Methods] 40 male SHRSP, eight-week-old, were randomly separated into 5 groups ( n = 8), including:①SHRSP control group,②) placebo treated group, ③valsartan treated group, ④ benazepril treated group, ⑤ combination treated group with valsartan and benazepril. In addition, 8 male Wistar-Kyoto rats (WKY), aged 8 wkkes, were used as control. MMP-2 protein expression in left ventricular myocardium of rats was detected by immunohistochemical staining. [Results] Systolic blood pressure (SBP), Left ventricular mass index (LVMI), CVF (collagen volume fraction) , PVCA (perivascular collagen area), and MMP-2 protein expression increased significantly in SHRSP compared with WKY, and decreased significantly after drug therapy. There were no differences in SBP, LVMI, CVF, PVCA, and MMP-2 protein expression between valsartan and benazepril group, but these indexes deceased more remarkably in the combination group than in the valsartan or benazepril group. [Conclusion] There is an increase in MMP-2 protein expression in the left ventricu- lar myocardium of SHRSP. After blockage of RAS, MMP-2 protein expression decreases remarkably in left ventricular myocardium of SHRSP. These effects may be in part responsible for the effect of be-nazepril or valsartan on reversing left ventricular remodeling. Benazepril/valsartan combination offers a better therapeutic effect on lowering SBP, and reversing ventricular remodeling in SHRSP than the treatment with either agent alone.