Changes of MMP-2,MMP-9 contents in cerebral tissues and cerebral edema in cerebral ischemia-reperfusion rats

Objective To investigate the expression and activation of MMP-2,MMP-9 in cerebral tissues of cerebral ischemia-reperfusion rats and the effects of doxycycline on the cerebral edema.Methods Cerebral ischemia-reperfusion model was established by middle cerebral artery occlusion(MCAO).The rats were randomly divided into a sham-operated and 6 reperfusion groups according to different reperfusion periods(3 h,6 h,12 h,24 h,72 h,and 120 h groups).Dry weight method was used to evaluate hemispheric water content of the ischemic side after treatment with doxycycline.Western blotting analysis and Gelatin zymography were used to determine the expression and activity of MMP-2 and MMP-9 in the ischemic cerebral tissues.Results The protein expression and activity of MMP-2 were significantly increased in the ischemia tissue at 3 h and 120 h after reperfusion(P 0.01) ;the protein expression and activity of MMP-9 began to increase at 6 h after reperfusion(P 0.01),reached the peak at 24 h,and then returned to the basal levels at 120 h after reperfusion(P 0.05).The hemispheric water content of the ischemic side gradually increased with reperfusion periods compared with the sham-operated group.Dexycycline significantly reduced the hemispheric water contents compared with the normal saline at the same time points(P 0.05 or P 0.01).Conclusion MMP-2,MMP-9 can induce vasogenic brain edema by degrading basal membrane of capillary vessel.The alteration of MMP-2,MMP-9 expression and activities are likely associated with brain edema during cerebral ischemia-reperfusion.