卡托普利与缬沙坦对兔动脉粥样硬化肾脏MMP-2及TIMP-2表达的影响

Effect of captopril and valsartan on expression of MMP-2 and TIMP-2 in kidney tissue of atherosclerotic rabbit

目的研究卡托普利与缬沙坦对兔动脉粥样硬化肾组织中基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)和组织金属蛋白酶抑制因子-2(tissue inhibitor of metalloproteinase-2,TIMP-2)表达的影响。方法30只雄性新西兰大白兔,随机分为4组:高脂饮食组(A组);高脂饮食加卡托普利组(B组);高脂饮食加缬沙坦组(C组);正常对照组(D组)。10周后B超检测造模成功,处死动物。取肾脏标本用免疫组化方法(SABC法)测定MMP-2和TIMP-2的表达。结果与对照组相比,高脂饮食组肾脏MMP-2水平明显降低;高脂饮食加卡托普利组MMP-2水平明显升高,但仍显著低于对照组;高脂饮食加缬沙坦组MMP-2水平明显升高,与对照组无显著差异。高脂饮食组肾脏TIMP-2表达显著高于对照组;高脂饮食加卡托普利组和高脂饮食加缬沙坦组较高脂饮食组TIMP-2明显降低,与对照组无显著差异,两组间也无显著差异。高脂饮食组MMP-2/TIMP-2比值显著低于对照组。结论动脉粥样硬化致兔肾脏局部MMP-2和TIMP-2表达发生的变化,与肾素-血管紧张素系统(renin angiotensin system,RAS)的激活有关,卡托普利和缬沙坦从不同水平阻断RAS后,可减轻MMP-2与TIMP-2表达的变化,达到保护肾脏的作用。

Objective To study the effect of captopril and valsartan on expression of matrix metalloproteinase-2（MMP-2） and tissue inhibitor of metalloproteinase-2 （TIMP-2） in kidney tissue of atherosclerotic rabbit. Methods Thirty male new zealand white rabbits were divided into four groups randomly： （A group ） cholesterol group, （B group ） cholesterol ＋ captopril treated group, （C group） cholesterol＋ valsartan treated group and （D group）control group. After 10 weeks, the expression of MMP-2 and TIMP-2 in renal tissue were examined by immunohistochemisrtry. Results Compared with control group, MMP-2 level of renal tissue in A group was decreased significantly. Captopri increased MMP-2, but the level of MMP-2 was still lower than that of control group. Also valsartan increased MMP-2,and there were no significant difference between the level of MMP-2 in C group and D group. TIMP-2 level of renal tissue in A group increased significantly compared to D group. Captopril and valsartan decreased the expression of TIMP-2 respectively. And there were no difference between B group and D group, C group and D group, and B group and C group. Conclusion The changes of the expression of MMP-2 and TIMP-2 in kidney tissue of atherosclerotic rabbit may be concerned with RAS activating. Captopril or valsartan could decreased the expression of those factors, so could ameliorate the lesions of renal injury through interruping RAS activiation.