大鼠实验性脑室出血后水通道蛋白1在脑内的表达及意义

目的 观察大鼠脑室出血后水通道蛋白1(AQP1)在大鼠脑内的表达变化,探讨其与脑出血后慢性脑积水之间的关系. 方法 将45只Wister大鼠按照随机数字表法分为3组:正常对照组(5只,不作任何处理)、假手术对照组(20只,侧脑室内注入0.1 mL生理盐水)、实验组(20只,侧脑室内注入0.1 mL枸橼酸化的自体静脉血),后2组再分别分为术后3 d、7 d、14 d、30 d4个时相点,每时相点5只.分别采用免疫组化、原位杂交方法观察大鼠脑室出血后不同时间AOP1蛋白及AQP1 mRNA在大鼠脑内的表达变化. 结果 实验组30 d时相点4只大鼠出现脑积水(4/5)、其余组别未出现慢性脑积水.正常对照组大鼠AQP1蛋白在脉络丛上皮细胞顶质膜强烈表达,室管膜、纵裂池、软脑膜、蛛网膜、硬脑膜也有较强烈表达;实验组大鼠脑室出血后3 dAQP1蛋白表达减少,7 d表达继续减少,14 d表达最弱,与正常对照组、假手术对照组比较,差异均有统计学意义(P<0.05),30d表达仍较弱.大鼠AQP1 mRNA在脑内的表达强度较AQP1蛋白弱,表达部位及变化与AQP1蛋白基本一致. 结论 AQP1作为水通道蛋白不仅参与脑脊液的分泌,可能也参与脑脊液的循环吸收过程;大鼠实验性脑室出血后AQP1表达下调导致脑脊液吸收减少可能也参与脑出血后慢性脑积水的形成.

Expression of AQP1 in rats after experimental intraventricular hemorrhage and its significance

Objective To explore the possible pathogenesis of chronic posthemorrhagic hydrocephalus by observing the expression of AQP1 on rats after experimental intraventricular hemorrhage. Methods Fourty-five rats were randomly divided into normal control(n=5),sham-operated(n=20)and experimental(n=20)groups.The 0.1mL saline and 0.1mL citrated autologous blood were injected into the lateral ventricle of the rats in the sham-operated and the experimental groups,respectively.The later two groups were divided into four subgroups according to different time points at 3,7,14 and 30 d(n=5).The change of protein expression of AQP1 at different time points of bleeding were detected by immunohistochemical techniques and that of mRNA expression of AQP1 was obsevred by in situ hybridization,respectively.and then,the possible pathogenesis of chronic posthemorrhagic hydrocephalus was discussed. Results At the time point of 30 d after intraventricular hemordmge,chronic hydrocephalus appeared in 4 rats(80%)in the experimental group.High protein expression of AQP1 was found in the apical of cuboidal epithelium of choroids plexus,the ependyma, the pia mater, the arachnoid and the dura in the normal control group;the protein expression of AQP1 gradually weakened in the experimental group 3 d aftea intraventricular hemorrhage and dropped to the bottom on the 14th d,which was significantly different from the normal control and sham-operative groups(P<0.05).The mRNA expression of AQP1 was weaker than the protein expression of AQP1,and the expression locations of them were basically in concordance. Conclusion AQP1 is involved not only in the secretion of cerebrospinal fluid,but also in the process of the CSF absorption.The decrease of CSF absorption induced by the decreased expression of AQP1 after intraventrieular hemorrhage in rats may also relate to the development of chronic posthemorrhagic hydrocephalus.