大鼠脑出血后MMP-2、MMP-9的表达与神经元凋亡关系的实验研究

The relationship between the expression of MMP-2,MMP-9 and the apoptosis of neurocyte after cerebral hemorrhage of rats

目的探讨脑出血后基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)的表达和血肿周围神经细胞凋亡发生情况之间的关系,以明确MMP-2、MMP-9对脑出血后神经细胞发生凋亡的贡献作用。方法80只雄性Wistar大鼠按照出血后的时间分成对照组和出血后6 h、12 h、1 d、2 d、3 d、6 d和10 d组,分别应用免疫组化和流式细胞仪方法检测血肿周围脑组织MMP-2、MMP-9的表达和神经细胞凋亡率,同时检测脑组织的含水量并进行脑出血动物的神经缺损评分,并统计这些指标的相关性。结果MMP-9,细胞凋亡率,神经功能缺损评分和脑组织含水量的动态变化均一致,脑出血后6 h开始升高,2 d达到高峰,10 d与对照组差异仍有统计学意义(P<0.05)。而MMP-2则是脑出血后1 d开始升高,6 d达到高峰,10 d后开始下降,与细胞凋亡率,神经功能缺损评分和脑组织含水量无明显相关性。结论神经细胞凋亡和脑组织含水量直接与神经功能缺损相关,而MMP-9的高表达则促进神经细胞的凋亡,脑组织含水量的增加。

Objective To investigate the relationship between the expression of MMP-2, MMP-9 and the apoptosis of neurocyte after intracerebral hemorrhage so that determine if the MMP-2 and MMP-9 contribute to the apoptosis of neurocyte. Methods Eighty rats were divided into control 6h, 12 h, 1 d, 2 d, 3 d, 6 d and 10 d groups after cerebral hemorrhage, the expression of MMP-2, MMP-9 and the rate of apoptosis of neurocyte were determined with immunohistochemistry and flow cytometry methods each, the water content and neurologic defect grade were carried out at the same time and analyze the correlation among them. Results MMP-9, the rate of apoptosis, water content and neurologie defect grade had same changed tendency, they began to increase at 6 h and attain the peak at 2 d after cerebral hemorrhage, the difference showed significance with control group at 10 d after cerebral hemorrhage （P〈0.05）, the MMP-2 began to increase at ld, attain the peak at 6 d and decrease at 10 d after cerebral hemorrhage, it had no correlation with the rate of apoptosis, water content and neurologic defect grade. Conclusion The apoptosis of neurocyte and water content of brain tissue show direct correlation with function of neurocyte. The high expression of MMP-9 can promote the apoptosis of neurocyte and increasing water content of brain tissue.