Doxycycline Attenuates Left Ventricular Remodeling And Improves Left Ventricular Function Through Inhibiting Matrix Metalloproteinases Inpost Myocardial Infarcted Rats

Objectives To observe the effects of doxycycline on the activity of matrixmetalloproteinase-2(MMP-2) and MMP-9, left ventricular remodeling and leftventricular function in the post myocardial infarction (MI) rats.Methods Total50male SD rats intraperitoneal injected with sodium pentobarbital (70mg.kg-1) anesthesia, after anesthesia, all of them with electrophysiology instrument monitoringECG, endotracheal intubation and connected to a breathing machine (Respiratory rate of45times per minute, tidal volume of30ml each time),34of them made into models of MI byligation of anterior descending coronary artery． Except the two died,32successfulmodeling,and then randomly divided into two groups：Model group, Doxycycline (DOC) group,with16rats each group．Remaining16rats undergoing thoracic surgery without ligaturinganterior descending coronary artery called sham-operated group. Three days later，rats in DOCgroup were intraperitoneally injected with doxycycline (15mg.kg-1.d-1,bid for5days), modelgroup were injected with saline solution (0.5ml bid*5days). Rats in sham-operated groupwere injected with saline solution (0.5ml bid*5days). Cardiac function were evaluated byechocardiography2weeks post MI,After echocardiography examination the rats were allkilled,and then open chest removed their heart tissue. Cardiac tissue went through the PBSbuffer rinse and removing adhered fat. We calculated heart weight to body weight ratio,expressed with HW/BW. Cardiac tissue was fixed after the myocardial tissue embedded inparaffin, made of the5μm thick slices,size of MI were analyzed by Masson staining method.Each group were taken six rat myocardium frozen tissue homogenate placed in Lysis buffer,centrifuged at12000rpm for15minutes and MMP-2, MMP-9activity were analyzed by gelatin enzymatic analysis.Results Compared with the model group, the left ventricular (LV) wall thicknessincreased significantly in DOC group, accompanied with the improvement of LVfractional shortening and LV ejection fraction (P<0.05, respectively), while the LVend-diastolic diameter was significantly reduced (P<0.05). Compared withSham-operated group,the HW，BW in Model group and Doxycycline group wereincreased, especially Model group were significantly increased,(P<0.05);Comparedwith Sham-operated group,HW，BW in Doxycycline group increased,(P<0.05),butreduced compared with the model group,(P<0.05).Infarct size reduced significantly inthe DOC group (P<0.05). The MMP-2, MMP-9activity in the DOC group wassignificantly decreased than the model group.Conclusion Doxycycline can improve rat heart function and attenuate left ventricularremodeling in post-MI rats through inhibiting MMP-2, MMP-9activity, reducing theinfarct size, alleviating myocardial fibrosis of the heart tissues.