凝血酶与实验性脑出血后水通道蛋白-4表达变化的研究

Experimental study on the relationship between thrombin and AQP-4 following cerebral hemorrhage

目的应用水蛭素拈抗凝血酶,探讨凝血酶与脑出血(intracerebral hemorrhage,ICH)后水通道蛋白-4(aquaporin-4,AQP4)表达的关系。方法健康大耳白兔,随机分为水蛭素干预组和对照组,每组出血后6h、12h、24h、2d、3d、5d各包括6只兔。RT-PCR法对AQP4 mRNA表达进行观察;Western blot法对AQP4蛋白表达进行观察。结果水蛭素干预组各时相AQP4 mRNA、AQP4蛋白表达均低于对照组。出血后12h、24h、2d与对照组相应时相比较有显著差异。结论凝血酶是脑出血早期导致AQP4 mRNA、AQP4蛋白表达增高的重要原因,其机制可能与低氧诱导因子(HIF-1)及凝血酶所致脑血肿周围细胞坏死有关。

Objective To study the relationship between thrombin and aquaporin-4（AQP-4） following cerebral hemorrhage. Methods Rabbits were divided into two groups：interfering with hirudin group （36 cases） and control group （36 cases）. Each group and each time phase （6h, 12h, 24h, 2d, 3d, 5d） involved 6 rabbits respectively. Then we detectd the changes of mRNA of AQP4 by RT-PCR and detected the changes of protein of AQP4 by western blot. Results There was obvious difference between the interfering with hirudin group and the control following cerebral hemorrhage for 12h, 24h and 2d. upregulation. Induction of hypoxia-inducible factor ble mechanism. Conclusion Thrombin is demonstrated to play a role in AQP4 mechanism.upregulation. Induction of hypoxia-inducible factor-1 （HIF-1） and cellular necrosis owing to thrombin is the possible mechanism.