Objective: To investigate the effects of preconditioning with doxycycline on ischemia/reperfusion (I/R) injury and expressions of matrix metalloproteinase-1 (MMP-1) and MMP-9 in myocardium in rat in vivo.
Methods: Sixty-four healthy male SD rats, weighing 300-350 g, were randomly divided into three groups: sham operation group (n = 16), I/R group (n = 24), and doxycycline preconditioning group (n = 24). The heart function, plasma level of creatine kinase (CK) and lactate dehydrogenase (LDH), and the activity of myeloperoxidase (MPO) were respectively determined in rat myocardium after ischemia for 60 minutes and reperfusion for 120 minutes or with the same procedure but with precondition of Doxycycline. Also the expressions of MMP-1 and MMP-9 was determined by immunohistochemistry.
Results: In I/R group, left ventricular systolic pressure (LVSP) and the maximum and minimum first derivative of LVSP (+/-dp/dtmax) were significantly less, and left ventricular end diastolic pressure (LVEDP), CK, LDH, the activity of MPO, and the protein expressions of MMP-1 and MMP-9 were remarkably higher compared with the sham operation group (P<0.05 or P<0.01). Heart function was improved, CK, LDH, MPO and the expressions of MMP-1 and MMP-9 were reduced obviously by doxycycline preconditioning compared with the I/R group (P<0.05 or P<0.01).
Conclusion: Precondition with doxycycline could remarkably abate I/R injury of rat myocardium in vivo and inhibit the expressions of MMP-1 and MMP-9.