Study On The Expression Of The Activated Mmp-9 In Rats Early After Experimental Cerebral Infarction

[Background and purpose] The extracellular matrix(ECM) is a multifunctional complex proteins and proteoglycans assembled in a highly organized manner that contributes to the structural integrity of cells and tissue within an organ system.The basement membrane,a special ECM,which provides structural support to the vasculature,is composed of ECM molecules such as type IV collagen,laminin,and fibronectin.In normal condition,ECM keeps in a dynamic balance through constant production and degradation.however,in certain pathological circumstances,the ECM is modulated such that the structure of the tissue becomes damaged or destroyed.Matrix metalloproteinases(MMPs) are a family of proteolytic enzymes that degrade the ECM and are implicated in numerous pathological conditions including atherosclerosis,inflammation, and tumor growth and metastasis etc.MMP-9(92-kDa type IV collagenase or gelatinase B) whose molecular weight is the heaviest in MMPs family plays a critical role in degradation of ECM including type I ,III,IV andV collagenases,gelatinases,elastins and fibronectins etc.It was reported in 3 ~~?~Fi~ 2001 recent studys that the early tissue injury after cerebral ischemia had relation to the up-regulation of MMP-9 gene express,but when onset of the activated MMP-9 is in argument.In addition,it is not yet reported whether assaying the MMP-9 level in plasma can reflect the expression of that in brain tissue or not.The present study is performed on basis of the foregoing questions. [Methods] Focal stroke was produced by permanent middle cerebral artery occlusion(MCAQ) by the suture method in the Sprague-Dawley rat, and the activated MMP-9 levels in tissue and plasma were measured by ELISA over a time course ranging from 2h to 1 6h. Meanwhile the praxiologic changes of the rats were observed as well as the morphologic ones observed after the brain slices at every time point were stained by TTC or HE.The data were analyzed by SPSS 10.0 for Windows. [Results] 1. Praxiology The rats undergoing artery occllusion over a different time course were characterized by praxiologic changes due to focal cerebral injury. 2. Morphology The brain slices at 2h time point revealed no neuron injury,however, cerebral infarction focus ,degeneration and necrosis of neurons were significantly observed at 6h, 1 6h,especially at 1 6h. 3. Biochemical changes The activated MMP-9 levels in brain tissue elevated 6h after cerebral infarction and reached a higher level,l4.68?.59u/mg, over a time course of 16h which was l.9-fold,2.2-fold higher than the values at 4 6h,2h(P<0.05),respectively.The levels in plasma were consistent with those in brain tissue and reached the highest value at 1 6h which was 2.7-fold,2.2-fold increase compared with those at 6h,2h (P<0.05),respectively.But the activated MMP-9 level in plasma at 6h didn抰 significantly elevate. [Conclusion] 1 .MMP-9 expression can be induced by early cerebral infarction.The activated MMP-9 levels in brain tissue begin to increase at 6h time point and reach a higher value at 1 6h.These serial changes are correponde...