The roles of matrix metalloproteinase and its inhibitor in ventricular remodeling after myocardial infarction in rats

Objective To study the role of doxycycline,which is the exogenous inhibitor of matrix metalloproteinase (MMPs),in left ventricular remodeling following myocardial infarction in rats.Methods Seventy rats were randomly divided into the groups of control(n=10), operation control(n=9), one day after myocardial infarction (MI) (n=10), one week after MI (n=10), two weeks after MI (n=8),four weeks after MI (n=7), treated with doxycycline for two weeks after MI (n=8) and treated for four weeks after MI (n=8). The activity of MMPs was measured by zymography and collagen amount by the method of chloramine T.The ratio of Ⅰ/Ⅲ collagen was assessed by immunohistochemical stain. Protein and mRNA of MMP-2,-9, TIMP-1 were determined by Western-Blot and RT-PCR. The cardiac function was measured by echocardiography (Acuson Sequoia 512). Results The activities and amounts of MMP-2,-9 decreased significantly,the mRNA of MMP-2, -9 reduced,the collagen amount decreased and the ratio of I/ Ⅲ increased in doxycycline groups as compered with infarction group. The amount of protein and mRNA of TIMP-1 did not change.Conclusions The effects of doxycycline on the activity of MMP-2,-9 may be one of the mechanisms which intervene in the ventricular remodeling following myocardial infarction.