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-α,IL-1β)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))(P0.01).Activities of MMP-2 and MMP-9,protein expression of MMP-2,MMP-9 and TIMP-2,and mRNA expression of MMP-2,MMP-9,TIMP-1,TIMP-2, IL-1β,and TNF-αwere all higher in carvedilol group compared with sham-operated group(P0.05).Compared with normal saline group,carvedilol group had lower LVEDP(P0.01),higher+dp/dt_(max),-dp/dt_(max)(P0.05),lower activities of MMP-2,MMP-9(P0.01),lower protein expression of MMP-2,MMP-9 and TIMP-2,and lower mRNA expression of MMP-2.MMP-9.TIMP-2,IL-1β,TIMP-1,and TNF-α(MMP-9 P0.01,others P0.05).Conclusion:Carvedilol can obvious ly decrease cardiac expression of MMP-2 and MMP-9 and slightly decrease expression of TIMPs;it can also decrease secretion of MMPs through decreasing IL-1βand TNF-αexpression,thus prevents myocardial extracellular matrix remodeling,reverses ventricular remodeling,and subsequently improves cardiac function.
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