Influence of a new endothelin receptor antagonist CPU-0213 on expression of MMPs mRNA and TIMPs mRNA in rats with hypertrophic myocardium induced by L-thyroxin / 中国临床药理学与治疗学

ABSTRACT

AIM: To observe the alterations of matrix metalloproteinases (MMPs) and TIMPs (the inhibitor of MMPs) and to study the influence of a new endothelin receptor antagonist CPU 0213 on MMPs mRNA and TIMPs mRNA in rats with hypertrophic myocardium induced by L thyroxin (L thy). METHODS: Male Sprague Dawley rats were randomly divided into three groups and sc administrated suspension of L thy ( 0.4 mg?kg -1 ?d -1 ) for consecutive 10 d except for normal group. On the 7th day, the rats treated with L thy were given CPU 0213(ig, 100 mg ? kg -1 ?d -1 ) for 3 d . The whole collagen content in myocardium was measured. Relative LV myocardial mRNA levels of MMPs (MMP 2, MMP 9) and tissue inhibitor (TIMP 1, TIMP 2) were detected with semi quantitative RT PCR. RESUITS The whole collagen content in myocardium induced by L thy decreased but it increased in the group CPU 0213. The expression of MMPs (MMP 2, MMP 9) mRNA was downregulated in L thy group and the expression of TIMPs mRNA was upregulated in L thy group markedly. Treated with CPU 0213, the expressions of MMP 9 and TIMP 1 mRNA were downregulated, whereas the expression of MMP 2 mRNA coming from CPU 0213 group tended to upregulate. But there was no statistical significance among these groups. CONCLUSION: CPU 0213 can inhibit the expression of MMPs and increase collagen content, which can improve heart function.