Doxycycline attenuates left ventricular remodeling and improves left ventricular function through inhibiting matrix metalloproteinases in post myocardial infarcted rats

Aim To observe the effects of doxycycline on the activity of matrix metalloproteinase-2(MMP-2) and MMP-9,left ventricular remodeling and left ventricular function in the post myocardial infarction(MI) rats.Methods A total of 48 male SD rats were randomly divided into three groups:sham-operated group,model group,doxycycline(DOC) group,with 16 rats in each group.Rats in model group and DOC group were made into models of MI by ligation of anterior descending coronary artery.Rats in DOC group were intraperitoneally injected with doxycycline(15 mg·kg-1·d-1,bid for 5 days),and those in model group were injected with saline solution(0.5 ml bid for 5 days).Rats in sham-operated group undergoing thoracic surgery without ligaturing anterior descending coronary artery were injected with saline solution(0.5 ml bid for 5 days).Cardiac function was evaluated by echocardiography 2 weeks post MI,and the size of MI was analyzed by Masson staining and MMP-2,MMP-9 activity was analyzed by gelatin enzymatic analysis.Results Compared with model group,the left ventricular(LV) wall thickness increased significantly in DOC group,accompanied with the improvement of LV fractional shortening and LV ejection fraction(P0.05,respectively),while the LV end-diastolic diameter was significantly reduced(P0.05).Infarct size was reduced significantly in the DOC group(P0.05).MMP-2,MMP-9 activity in DOC group was significantly decreased than that in the model group.Conclusion Doxycycline improves rat heart function and attenuates left ventricular remodeling of post-MI rats to a certain extent through inhibiting MMP-2,MMP-9 activity,reducing the infarct size,and alleviating myocardial fibrosis of the heart tissues.