白藜芦醇对大鼠脑缺血基质金属蛋白酶-9及其组织抑制因子-1表达的影响

The effect of resveratrol on expression of MMP-9 and TIMP-1 in the experimental focal cerebral ischemia

目的探讨白藜芦醇在大鼠局灶性脑缺血再灌注损伤中对脑水肿的影响,及对基质金属蛋白酶-9(MMP-9)和基质金属蛋白酶组织抑制因子-1(TIMP-1)表达的影响。方法将健康雄性Wistar大鼠105只,随机分为假手术组(5只)、缺血再灌注组(对照组,50只)和白藜芦醇药物干预组(药物组,50只)。采用线栓法制作大鼠大脑中动脉闭塞模型,使用干湿重法测定脑含水量,免疫组织化学法观察MMP-9和TIMP-1的表达。结果药物组与对照组比较,脑组织含水量在缺血再灌注1、2、3天明显减轻,MMP-9和TIMP-1的表达在缺血再灌注1、2、3天明显减少,TIMP-1在再灌注6 h时亦减少,两组比较差异有显著性意义(P<0.05)。结论在缺血再灌注所致的血管损伤中白藜芦醇具有脑保护作用,通过抑制MMP-9的表达而减轻脑水肿,调节MMP-9和TIMP-1的活性可能是其作用机制之一。

Objective To study the effect of resveratrol on cerebral of matrix metalloproteinase-9 （MMP-9） and tissue inhibitor edema as well as the expression of matrix metalloproteinase-1 （TIMP-1） after the focal cerebral ischemia-reperfusion injury in rat. Methods 105 male Wistar rats were randomly divided into 3 groups： sham-operated group of 5 rats, ischemia-reperfusion group （control group） of 50 rats and resveratrol group of 50 rats. The middle cerebral artery occlusion model was constructed by Longa＇s method. The expression of MMP-9 and TIMP-1 was investigated with immunohistochemistry and the water content was calculated with dry and wet weight method after 6 h, 1,2,3 and 7 d of reperfusion. Results MMP-9 and TIMP-1 were not expressed in the sham-operated group, The water content, the expression of MMP-9 and TIMP-1 were significantly decreased in resveratrol group compared with the control group after 1,2 and 3 d of reperfusion,and the expression of TIMP-1 was also significantly decreased at 6 h of reperfusion. Conclusion Resveratrol has a neuroprotective effect on the ischemic brain. This effect may be related to the inhibition of expression of MMP-9 and TIMP-1.