摘要
目的探讨阿利吉仑对大鼠心肌梗死后左室重构的影响及作用机制。方法 60只Wistar大鼠随机分为假手术组、模型对照组、培哚普利组和阿利吉仑组,每组15只。除假手术组外,其他3组均制作心肌梗死模型。培哚普利组和阿利吉仑组制作心肌梗死模型后分别给予培哚普利和阿利吉仑共8周。酶联免疫吸附测定(ELISA)检测血清中高敏C-反应蛋白(hs-CRP),免疫组织化学方法检测基质金属蛋白酶(MMP)-2、MMP-9、金属蛋白酶抑制因子(TIMP)-1和转化生长因子-β(TGF-β)的表达。逆转录聚合酶链反应(RT-PCR)检测心肌组织MMP-2、MMP-9、TIMP-1、TGF-β、CollagenⅠ和ⅢmRNA的表达。Western blotting检测心肌组织MMP-2、MMP-9、TIMP-1、TGF-β蛋白的表达。结果培哚普利组和阿利吉仑组血清hs-CRP明显低于模型对照组(P<0.05)。培哚普利组和阿利吉仑组MMP-2、MMP-9、TGF-β、CollagenⅠ和ⅢmRNA和蛋白的表达明显低于模型对照组(P<0.05),TIMP-1 mRNA的水平则高于模型模型对照组(P<0.05)。结论阿利吉仑通过下调MMP-2、MMP-9、TGF-β、CollagenⅠ和Ⅲ和hs-CRP表达、上调TIMP-1表达发挥作用。阿利吉仑和培哚普利在减轻大鼠心肌梗死后左室重构无明显差别。
Objective To investigate the effects of aliskiren on ventricular remodeling in rats with acute myocardialinfarction （AMI） and the related mechanism. Methods Sixty male Wistar rats were randomly assigned into four groups （n =15）：sham group, control group, perindopril group and aliskiren group. After ligation of the anterior descending coronary artery,the rats in perindopril group and aliskiren group were given perindopril or aliskiren for 8 weeks, respectively. The concentration of hs-CRP in serum was assayed by ELISA. The expression of MMP-2, MMP-9, TIMP-1 and TGF-β was detected by immune-histochemistry. The mRNA expression of MMP-2, MMP-9, TIMP-1, TGF-β, Collagen Ⅰand Ⅲ was determined by RT-PCR.Protein expression of MMP-2, MMP-9, TIMP-1 and TGF-β was determined by Western blotting. Results The concentration ofhs-CRP was significantly lower in perindopril group and aliskiren group than in the control group （ P〈0. 05）. The mRNA andprotein expression of MMP-2, MMP-9, TGF-β, Collagen Ⅰ and Ⅲ were significantly down-regulated in perindopril group andaliskiren group as compared to the sham group （P〈0. 05）. Meanwhile, the mRNA and protein expression levels of TIMP-1 weresignificantly up-regulated in perindopril group and aliskiren group as compared to those in sham operated group （ P〈0. 05）. Conclusion Aliskiren can downregulate the expression of MMP-2, MMP-9, TGF-β, Collagen Ⅰand Ⅲ and hs-CRP,upregulate TIMP-1. There is no significant difference between perindopril and aliskiren in ventricular remodeling in rats with AMI.
出处
《医药导报》
CAS
北大核心
2014年第2期167-172,共6页
Herald of Medicine
关键词
阿利吉仑
心肌梗死
急性
左室重构
Aliskiren
Myocardial infarction, acute
Ventricular remodeling
