尼美舒利对大鼠脑出血后脑水肿及基质金属蛋白酶2的影响

Effect of nimesulide on cerebral edema and metallopotei-nase-2 in rat brain after intracerebral hemorrhage.

目的探讨尼美舒利对脑出血(ICH)后脑组织炎症损害的保护作用。方法 150只SD大鼠随机分为尼美舒利治疗组、ICH组和假手术组,每组50只。术后每组分5个时间点(各10只)。立体定向自体血注入尾状核建立ICH模型;观察各组各时点血肿周围脑组织环氧化酶2(COX-2)和基质金属蛋白酶2(MMP-2)动态表达,测定血肿周边及脑组织含水量。结果 ICH组各时点COX-2和MMP-2蛋白表达明显高于假手术组,ICH组各时点含水量与COX-2和MMP-2蛋白表达呈正相关,COX-2蛋白表达与MMP-2蛋白表达呈正相关。尼美舒利组治疗COX-2、MMP-2蛋白表达低于ICH组,各时间点脑组织含水量低于ICH组。结论尼美舒利能抑制COX-2蛋白表达,同时直接或间接影响MMP-2蛋白表达,减轻脑水肿,抗炎治疗可能是治疗脑出血后脑水肿的一个新途径。

Objective To explor the protective effect of nimesulide on inflammation of brain tissue damage after cerebral hemorrhage（ICH）.Methods In this study,150 SD rats were randomly assiged to treatment group,ICH group and the sham-operated group.The changes of every index were measured respectively after operation at time stages 6h,12h,24h,72h,7d in every group.There were 10 rats in every time stage.we induced intracerebral hemorrhage in rats by injecting autologous blood into the left caudate nucleu.Through immunohistochemistry（IHC）dyeing,the brain tissue slices were computed by the method of the positive cell measure and the changes of the contents of COX-2 and MMP-2 protein were measured.Tissues weight of rats brain perihematoma were measured by dry and wet method.Results In ICH group,the contents of COX-2 protein and MMP-2 protein were significantly higher than sham operation group.In ICH group,water contents were positively correlated with COX-2 and MMP-2,the changes of the COX-2 protein were positively correlated with the changes of the MMP-2 protein.The contents of COX-2 and MMP-2 in the ICH group were significantly higher than the treating group.In ICH group,the water contents were significantly higher than the treating group.Conclusion Nimesulide could inhibit the expression of COX-2 and MMP-2 in ICH,and decreased the water contents in perihematoma.Nimesulide may inhibit the expression of MMP-2 through the mechanisms of COX-2.It shows that nimesulide has protective effects in ICH.