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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 investigate the effect of lysophosphatidic acid on the permeability of the blood-brain barrier and the expression of aqaporin-4 (AQP4) in rats. Methods A total of 50 uL lysophosphatidic acid was injected into the right caudal putamen of rats under stereotaxic apparatus. Immunohistochemical staining of AQP4 protein in adjacent brain tissues was performed at different time points. Evans blue (EB) Tracer was used to determine the blood-brain barrier (BBB) permeability at different time points. Results The expression of AQP4 protein in the putamen began to increase 6 h after injection of lysophosphatidic acid and peaked on the 2nd day, and remained at the 3rd day and then gradually decreased. Increased expression of the site mainly for microvascular endothelial cells and the surrounding glial cells. Compared with the control group at each time point, there was a significant difference; BBB on the ipsilateral caudate putamen began to increase EB permeability at 6h after LPA injection, reaching the maximum at 24h and decreasing gradually at 48h, The difference was significant (p <0.05). Conclusion Lysophosphatidic acid can promote the increase of AQP4 protein expression in brain microvascular endothelial cells and surrounding glial cells, cause the increase of blood-brain barrier permeability, and participate in the occurrence of cerebral edema.