溶血磷脂酸对大鼠uPA蛋白的表达及其对血脑屏障的影响

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

目的研究溶血磷脂酸对uPA蛋白表达及其对血脑屏障的影响。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,免疫组化检测不同时间点注射部位邻近脑组织uPA蛋白表达,伊文思蓝(EB)作为示踪剂定量测定相应时间点BBB通透性。结果注射溶血磷脂酸6h后尾壳核uPA蛋白表达开始增高,在24h达高峰,48h以后逐渐下降,与对照组相同时间点比较差异有显著性(P<0.05),同侧基底节区BBB对EB的通透性6h开始增加,24h通透性达最大,到48h通透性渐减,与对照组相同时问点比较差异有显著性(P<0.01)。结论溶血磷脂酸可能促进脑微血管内皮细胞及其周围星形胶质细胞uPA蛋白表达的增加,降解基底膜,破坏血脑屏障,从而促进脑水肿的发生。

Objective To study the effect of lysophosphatidic acid on the expression of uPA 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 uPA at different time points was detected by immunohistochemical method; Evans Blue（EB） was used to quantitatively measure the permeability of BBB at reciprocal time points. Results Six hours after injection of 50uL lysophosphatidic acid,the uPA expression began to increase,and reached the peak level on the first day, then decreased slowly, compared with the same time points of control group, the difference was significant（P〈0. 05）. The permeability of BBB began to increase at 6h point after LPA was 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. 01 ）. Conclusions Lysophosphatidic acid can induce the upregulation of uPA protein of the endothelial cells of brain microvessels and astrocytes around them, leading to degradation of basement membrane and brain edma.