实验性脑出血灶周MMP-9的表达与脑水肿的关系

Expression of MMP-9 in tissue around experimental cerebral homorrhagic focus and its relation with brain edema

目的探讨脑出血(ICH)后出血灶周脑组织MMP-9表达的动态变化,分析其与脑水肿的关系。方法健康雄性Sprauge-Dawley(SD)大鼠56只,分为正常组(8只)和手术组(48只),手术组选择出血后12、24、48、72、96、120h共6个时间点,每点各8只。在脑立体定向仪下采用自体动脉血注入尾状核法制备脑出血模型。用免疫组化法和RT-PCR法检测MMP-9的表达水平;用干湿重法测量脑含水量(BWC);用测定渗出脑血管外的EB量来评价BBB的通透性,电镜观察神经元形态变化。结果ICH灶周脑组织MMP-9的表达在48h达峰值,脑水肿于72h达峰值,两者呈正相关(r=0.698,P<0.01)。电镜观察到血管周围水肿,神经元水肿。结论MMP-9参与了ICH后灶周脑组织水肿的过程,诱导或加重脑水肿。

Objective To explore the dynamic changes of MMP-9 in tissue around hemorrhagic focus, and to analyze the relation between the changes and brain edema. Methods Fifty-six healthy male SD rats were randomly divided into normal group and operation group. In operation group six time points of 12,24,48,72,96 and 120 h after ICH were chosen and eight rats for each time point. ICH model of rat was induced by using stereotactic infusion autologous blood 70/11 into the right caudate nucleus. The expression of MMP-9 was detected by immunohistochemical method and RT-PCR. Brain water content（BWC） was determined by comparison of wet and dry weight. The BBB opening was evaluated by the Evans Blue extravasation method. Pathological changes were observed with transmission electron microscope. Results The expression of MMP-9 in tissue around cerebral hemorrhagic focus reached a peak at 48 h. The brain water content reached a peak at 72 h, and it was synchronous with the level of MMP-9 and there was a positive correlation between them （r = 0. 698, P〈0. 01 ）. Brain edema was observed with transmission electron microscope. Conclusions MMP-9 participates the brain edema process. It induces or aggravates brain edema.