Effects Of 5(s), 6(r)-lipoxin A₄ Methyl Ester On The Permeability Of Blood-brain Barrier In Rats After Focal Cerebral Ischemia-reperfusion

【Objective】To investigate the effects of 5(S),6(R)-lipoxin A₄ methyl ester (LXA₄ ME) on the permeability of blood-brain barrier(BBB) in rats after cerebral ischemia-reperfusion,and to discuss the possible mechanism of its protective effects.【Methods】Seventy-two adult male Sprague-Dawley rats weighing 200～250 g were randomly divided into 3 groups (n=24 each): sham operation group (Sham);cerebral ischemia-reperfusion group (I/R) and LXA₄ ME group (LXA₄ ME). Focal cerebral ischemia was produced by improved thread occlusion of right middle cerebral artery. After 2 h of arterial occlusion, blood flow was restored by withdrawal of the nylon suture. After 24 h of reperfusion, the neurological deficit was assessed by the method of Longa's score. The histopathological change was observed after HE staining. The brain water content were measured by detecting the wet weight and dry weight. BBB permeability was assessed by fluorescence spectrophotometer and fluorescence microscopy for evans blue (EB) extravasation. The expression and activity Of matrix metalloproteinase-9 (MMP-9) in different group was detected by immunohistochemical staining,Western blot and gel gelatin zymography.【Results】The neurologic deficit scores, the brain water content, EB content and MMP-9 protein expression and activity in the cortex were significantly higher and brain tissue injury was more severely than those in the sham group; the above-mentioned cerebral ischemia-reperfusion induced changes were significantly ameliorated in LXA₄ ME group.【Conclusion】LXA₄ ME can improve functional recovery, protect BBB against cerebral ischemia-reperfusion injury ,decrease brain edema .The mechanism may be by inhibiting MMP-9 protein expression and activity in the brain tissue.