Effect of carvedilol on cardiac metalloproteinases and tissue inhibitors of metalloproteinases after myocardial infarction in rats / 第二军医大学学报

ABSTRACT

Objective:To investigate the effect of carvedilol on expression of cardiac matrix metalloproteinases(MMPs)and tissue inhibitors of metalloproteinases(TIMPs)after myocardial infarction in rats.Methods:An animal model of acute myocar- dial infarction(AMI)was established by descending left coronary artery ligation in 24 rats and they were divided into carvedilol (10 mg?kg~(-1)?d~(-1))group(n=12)and normal saline group(n=12).Sham operated group(n=9)received the same proce- dure but with no ligation.All animals were treated for 6 weeks via a gastric lavage.Heart function and hemodynamic parame- ters were determined after 6 weeks.The protein expression of cardiac MMP-2,MMP-9 and TIMP-2 was detected by immuno- histoehemical analysis in AMI groups,and the MMPs activities were assessed by zymography.Gene expression of myocardial MMPs/TIMPs(MMP-2,9 and TIMP-1,2)and cytokines(TNF-?,IL-1?)were measured by real-time quantitative PCR.Re- suits:Compared with Sham-operated group,earvedilol group had significantly higher left ventricular end-diastolic pressure(LV- EDP)and lower LV upstroke velocity(+dp/dt_(max))and LV descent velocity(-dp/dt_(max))(P