The Effect Of Matrix Metalloproteinase-2 And Matrix Metalloproteinase-9 On Skeletal Muscle Ischemia Reperfusion Injury

objective: Doxycycline, blocking the function of MMP-2 and MMP-9,was used to investigate the role of MMP-2 and MMP-9 and their antagonist,doxycycline, in skeletal muscle ischemia-reperfusion injury(SMIRI). Methods: Twenty-four healthy male Sprague-Dawley rates, weighing 250 to 300g, were selected and randomly devided into group A, B, and C.Rats in the group A underwent anesthetization and external jugμlar vein cannμlation alone; Rats in the group B underwent twice-daily gavage with 2ml normal solution for 7 days prior to the induction of 4h ischemia to the left hindlimb,followed by 4h reperfusion.Rats in the group C were treated by twice-daily gavage with doxycyline (50mg/kg in 2ml water) for 7 days prior to the induction of 4h ischemia to the left hindlimb,followed by 4h reperfusion.Levels of MMP-2 mRNA and MMP-9 mRNA of skeletal muscle were determined by reverse transcription-polymerase chain reaction.The levels of lactate dehydrogenase(LDH), creatine kinase(CK), malondialdehyde(MDA) in the plasma and the myeloperoxidase(MPO) activity in skeletal muscle were measured by colorimetry respectively.The oedema degree was quantified by calculating the wet/dry weight ratio of skeletal muscle.Skeletal muscle were also observed histologically and ultrastructurally.Ruslts: SMIRI contributed to increase the level of MMP-2 and MMP-9 mRNA in skeletal muscle.The level of CK, LDH, MDA, MPO and wet/weight ratio increase significantly. The levels of MMP-2 and MMP-9 mRNA, CK, LDH, MDA, MPO and wet/dry weight ratio were remarkedly decreased after the gavage of doxycycline and thus the pathological injuries were attenuated in skeletal muscles. Conclusion: SMIRI enhanced the synthesis of MMP-2 and MMP-9,which induced the injury of skeletal muscle.Doxycycline reduced SMIRI by blocking the function of MMP-2 and MMP-9.