卡托普利对自发性高血压大鼠心脏MMP-9和TIMP-1表达的影响

Effect of Captopril on expression of cardiac matrix metalloproteinases-9 and tissue inhibitor of metalloproteinase-1 in spontaneously hypertensive rats

目的观察卡托普利对自发性高血压大鼠(SHR)心脏基质金属蛋白酶-9(MMP-9)和基质金属蛋白酶抑制剂-1(TIMP-1)表达的影响。方法将16只14周龄雄性SHR随机平分为卡托普利组和对照组,另以8只同龄雄性SD大鼠作为正常对照组。卡托普利组以卡托普利100mg/(kg·d)灌胃,SHR对照组不灌药,于灌药12周后麻醉下取出大鼠心脏。取左室心肌组织分别进行免疫组化分析MMP-9、TIMP-1、CollagenⅠ和Ⅲ的表达;RT-PCR检测MMP-9和TIMP-1mRNA表达;MASSON染色测量胶原容积分数(CVF);碱水解法测定羟脯氨酸(Hypro)含量。结果①SHR对照组左室重量指数(LVI),左室CVF、Hypro、MMP-9、TIMP-1、CollagenⅠ和Ⅲ的表达明显高于正常对照组(P<0.01);相对于SHR对照组,卡托普利组各参数则显著降低(P<0.05)。②MMP-9和TIMP-1与上述指标呈高度正相关(P<0.01)。结论MMP-9和TIMP-1与SHR心肌纤维化密切相关,卡托普利能抑制MMP-9和TIMP-1的表达。

[Objective] To observe the effect of Captopril on the expression of cardiac MMP-9 and TIMP-1 of Spotitaneously Hypertensive Rats. [Methods] 16 fourteen-week-old male SHRs were randomly assigned to Captopril and control group equivalendy. 8 same age male SD rats were treated as normal control group. A daily dose of 100 mg/（kg-d） Captopril were given to Captopril group for 12 weeks by garage. MMP-9, TIMP-1, Collagen Ⅰ and Ⅲ were evaluated by immunohistochemistry and RT-PCR. CVF was measured by MASSON staining. The concentration of Hypro was detected by Alkaline hydrolysis method. [Re.suits] The LVI, CVF, Hypro and the expression of cardiac MMP-9, TIMP-1, Collagen Ⅰ and Ⅲ of SHR control group were significantly higher than those of normal control group （P 4）.01）. Compared with SHR control group, these indices of Captopril group decreased obviously （P 〈0.05）. [Conclusions] MMP-9 and TIMP-1 is closely related with myocardial fibrosis of SHR and suppressed by Captopril.