凝血酶抑制剂nexin-1对大鼠脑出血后脑水肿的保护作用机制的研究

摘要

Objective:To explore the protective effect mechanism of thrombin inhibitor nexin-1 on brain edema after intracerebral hemorrhage.Method:90 rates were randomly divided into the control group, the model group and the intervention group.The model of cerebral hemorrhage was made by caudate nucleus injection of autologous arterial blood. In the modeling process,the intervention group was injected with thrombin inhibitor nexin-1 in the caudate nucleus, the rest group were injected with Normal Saline.12 hours, 24 hours and 36 hours after the injection,the PAR-1 in brain tissues was detected by immunohistochemistry, the Caspase-3,Claudin-5 and ZO-1 in brain tissues were detected by western blotting method.Result:The PAR-1 and Caspase-3 in brain tissues of the model group were significantly higher than those of the control group and the intervention group,the differences were statistically significant(P<0.05). The Claudin-5 and ZO-1 in brain tissues of the model group were significantly lower than those of the control group, the Claudin-5 and ZO-1 in brain tissues of the intervention group were significantly higher than those of the model group, the differences above were all statistically significant(P<0.05).Conclusion:The protective effect mechanism of thrombin inhibitor nexin-1 on brain edema after intracerebral hemorrhage may through reducing the expression of PAR-1, Caspase-3 and increasing the expression of Claudin-5 and ZO-1 to achieve.%目的：探讨凝血酶抑制剂nexin-1对大鼠脑出血后脑水肿的保护作用机制。方法：将90只大鼠采用随机数字表法分为对照组、模型组和干预组，采用尾状核注射自体动脉血的方法复制脑出血模型，在造模的过程中往干预组尾状核部位注射凝血酶抑制剂nexin-1，其余组注射生理盐水。在给药12、24 h和36 h后，采用免疫组化法检测脑组织中的PAR-1，采用Western blotting法检测脑组织中的Caspase-3、Claudin-5和ZO-1。结果：模型组脑组织中PAR-1和Caspase-3的表达程度高于对照组及干预组，比较差异均有统计学意义（P<0.05）；模型组脑组织中的Claudin-5和ZO-1的表达水平低于对照组（P<0.05），干预组脑组织中的Claudin-5和ZO-1的表达程度高于模型组，以上比较差异均有统计学意义（P<0.05）。结论：凝血酶抑制剂nexin-1对大鼠脑出血后脑水肿的保护作用可能是通过降低脑组织中PAR-1、Caspase-3的表达以及升高脑组织中Claudin-5和ZO-1的表达来实现的。