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(1)
【摘要】 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。
, 百拇医药 【关键词】 nexin-1； 脑出血； 脑水肿； PAR-1； Caspase-3； Claudin-5； ZO-1
Protective Effect Mechanism Study of Thrombin Inhibitor Nexin-1 in Brain Edema after Intracerebral Hemorrhage in Rats/CHEN Hong-qin.//Medical Innovation of China，2015，12(26)：025-028
【Abstract】 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.
, http://www.100md.com
【Key words】 Nexin-1； Cerebral hemorrhage； Brain edema； PAR-1； Caspase-3； Claudin-5； ZO-1
First-author’s address：Panshi Hospital of Caoxian，Caoxian 274400，China
doi：10.3969/j.issn.1674-4985.2015.26.008
脑出血在临床中有较高的死亡率和致残率，研究表明脑出血后会并发有严重的炎症反应、脑细胞毒性损伤、脑水肿等，其中脑水肿是脑出血最为常见和最为严重的并发症[1]。研究证实脑出血后大量产生的凝血酶会对大脑产生毒性作用并会引起脑组织产生严重的水肿[2]。Caspase-3是机体中特异性的死亡信号转导分子，在细胞凋亡的过程中起到非常重要的作用[3]。有研究表明血脑屏障通透性的异常增加与血脑屏障中的紧密连接复合体的异常变化有关，而Claudin-5和ZO-1是紧密连接复合体重要的组成部分[4-5]。凝血酶抑制剂nexin-1是一种内生的丝氨酸蛋白水解酶，能迅速的抑制凝血酶的表达及活性[6]。本课题组的前期研究已经证实凝血酶抑制剂nexin-1对大鼠脑出血后脑水肿有保护作用，但对于凝血酶抑制剂nexin-1对大鼠脑出血后脑水肿的保护作用的机制还未清楚。因此本文通过检测nexin-1干预脑出血大鼠后相关活性因子水平，来探讨nexin-1保护大鼠脑出血后脑水肿的作用机制，现报道如下。, http://www.100md.com(陈洪芹)
, 百拇医药 【关键词】 nexin-1； 脑出血； 脑水肿； PAR-1； Caspase-3； Claudin-5； ZO-1
Protective Effect Mechanism Study of Thrombin Inhibitor Nexin-1 in Brain Edema after Intracerebral Hemorrhage in Rats/CHEN Hong-qin.//Medical Innovation of China，2015，12(26)：025-028
【Abstract】 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.
, http://www.100md.com
【Key words】 Nexin-1； Cerebral hemorrhage； Brain edema； PAR-1； Caspase-3； Claudin-5； ZO-1
First-author’s address：Panshi Hospital of Caoxian，Caoxian 274400，China
doi：10.3969/j.issn.1674-4985.2015.26.008
脑出血在临床中有较高的死亡率和致残率，研究表明脑出血后会并发有严重的炎症反应、脑细胞毒性损伤、脑水肿等，其中脑水肿是脑出血最为常见和最为严重的并发症[1]。研究证实脑出血后大量产生的凝血酶会对大脑产生毒性作用并会引起脑组织产生严重的水肿[2]。Caspase-3是机体中特异性的死亡信号转导分子，在细胞凋亡的过程中起到非常重要的作用[3]。有研究表明血脑屏障通透性的异常增加与血脑屏障中的紧密连接复合体的异常变化有关，而Claudin-5和ZO-1是紧密连接复合体重要的组成部分[4-5]。凝血酶抑制剂nexin-1是一种内生的丝氨酸蛋白水解酶，能迅速的抑制凝血酶的表达及活性[6]。本课题组的前期研究已经证实凝血酶抑制剂nexin-1对大鼠脑出血后脑水肿有保护作用，但对于凝血酶抑制剂nexin-1对大鼠脑出血后脑水肿的保护作用的机制还未清楚。因此本文通过检测nexin-1干预脑出血大鼠后相关活性因子水平，来探讨nexin-1保护大鼠脑出血后脑水肿的作用机制，现报道如下。, http://www.100md.com(陈洪芹)