溶血磷脂酸对血脑屏障及AQP4蛋白表达的影响  

Effect of lysophosphatidic acid on blood-brain barrier permeability and the expression of AQP4

作　　者：阮清源[1] 张兆辉[1] 李毅亮[1] 邱利君[1] 宋金春[2] 汪宁[1] 李慧[1] 

机构地区：[1]武汉大学人民医院神经内科,430060 [2]武汉大学人民医院药剂科,430060

出　　处：《卒中与神经疾病》2009年第2期90-93,共4页Stroke and Nervous Diseases

摘　　要：目的研究溶血磷脂酸对大鼠血脑屏障通透性及水孔蛋白-4(aqaporin-4,AQP4)表达的影响。方法在立体定向仪下向大鼠右侧尾壳核注射50uL溶血磷脂酸,在不同时间点对注射部位邻近脑组织AQP4蛋白进行免疫组化检测;用伊文斯蓝(Evans blue,EB)作为示踪剂定量测定不同时间点血脑屏障(Blood-brain barrier,BBB)通透性。结果注射溶血磷脂酸后6h尾壳核AQP4蛋白表达开始增高,在第2d达到高峰,并维持到第3d,以后逐渐下降。表达增高的部位主要为微血管内皮细胞及其周围的胶质细胞。与对照组各时间点相比,均有显著性差异;LPA注射后6h同侧尾壳核区BBB对EB通透性开始增加,24h达最大,到48h逐渐减低,与对照组相同时间点比差异有显著性(p<0.05)。结论溶血磷脂酸可以促进脑微血管内皮细胞及其周围胶质细胞AQP4蛋白表达的增加,引起血脑屏障通透性的增加,参与脑水肿的发生。Objective To study the effect of lysophosphatidic acid on the expression of AQP4 （aquaporin-4） and the blood-brain barrier permeability. Methods After the experimental SD rats were fixed in the stereotaxic frame, 50uL lysophosphatidic acid was injected into the right caudate nucleus and the expression of AQP4 was detected by immunohistochemical method;Evans Blue（EB） was used to quantitatively measure the permeability of BBB at different time points. Results Six hours after injection of 50uL lysophosphatidic acid, the AQP4 expression began to increase, and reached the peak level on the second day. The peak sustained to the third day,then decreased slowly, and the predominent region was the endothelial cells of mieosoftvessels and compared with the same time points of control group, the difference was significant. The permeability of BBB began to increase at 6h point after LPA administered into ipsilateral caudate nucleus, and reached the peak at 24h. Then the permeability of BBB grandully lowered after 48h. In comparision with the same time points of control group, there was significant difference（p〈0. 05）. Conclusions Lysophosphatidic acid can induce the upregulation of AQP4 protein aroud the brain microvessels,lead to the desruption of BBB, and may participate in the pathologic mechanism of brain edema formation.

关 键 词：溶血磷脂酸 水孔蛋白-4 血脑屏障 

分 类 号：R742[医药卫生—神经病学与精神病学]