大鼠急性脑缺血再灌注细胞毒性水肿与水通道蛋白-4表达

Expression of aquaporin-4 during cytotoxic edema after cerebral ischemic reperfusion in rats

目的观察大鼠急性脑缺血再灌注细胞毒性水肿与AQP4的表达水平的变化的相关性。方法为假手术组;B组:32只,为缺血再灌注组)。两组随机配对行DWI和T2WI MR检查后处死,脑组织切片免疫组化染色观察AQP-4于不同时间点在梗死区及对侧镜像区的表达。结果B组MCAO后15min即在DWI上出现缺血区高信号;再通后高信号区缩小。可恢复的缺血区拔栓前的rADC平均(69.3±16.4)%;未能恢复的核心区平均(47.6±18.5)%。免疫组化染色显示B组MCAO1h内AQP-4阳性神经细胞△S快速上升。恢复再通后至24h,梗死边缘区移行带阳性细胞明显减少,△S持续下降;梗死中央区阳性细胞缓慢增加,△S缓慢上升。B组拔栓前△S和DWI高信号面积(rs-DWI)均与时间呈线性关系,但再灌注后24h内两项指标均与时间无线性相关。结论脑缺血再灌注状态下AQP-4表达增强与超早期细胞毒性水肿(<1h)以及梗死的形成有关。它也是超早期脑缺血组织rADC值下降,形成DWI上高信号的分子机制之一。

Objective To investigate the role of the aquapofin-4 （AQP-4） expression in cytotoxic edema after cerebral ischemic reperfusion （CIR） .Methods CIR models were established by occluding unilateral middle cerebral arteries（MCA） of rat with nylon filament.48 SD rats were divided into 2 groups randomly,including false operation group A （ n = 12） and operation groupB （blood flow blocked 1 hours and the reperfusion for 24 h, n = 24）.Both groups were examined with DWI and T2WIMRI.The relative ADC （rADC）, relative density （rd）, and relative area （rs） of the biggest hyperintensity signal layer on DWI were measured. Then the animals were sacrificed and perfnsed with the mixture solution consisting of TTC at different time intervals. The AQP-4 expression was measured with the Image Analyzer.Meanwhile,histologie examination was performed at each group.Results In the operation group, abnormal high intensity was found in DWI of ipsilateral MCA territory at 15 rain after MCAO, and rADC value decreased quickly within 1 h after MCAO, while the AQP-4 expression,the rd-DWI, and the rs-DWI increased rapidly in the stage. With the progress of the time after reperfusion,the rADC value increased slowly flU 24 h,and the rs-DWI decreased rapidly in the stage.While the AQP-4 expression （△S） decreased rapidly in the penumbra but increased still in the center area. Conclusion The high expression of AQP-4 in the acute iscliemic cerebral tissues played a significant role in the cytotoxic edema. Certainly, it was also one of the important reasons of the decrease of rADC and hyperintensity on DWI in the early stage of the cerebral ischemia.