溶血磷脂酸对血脑屏障通透性的影响及其机制  

Effect of lysophosphatldic aeid on blood-brain barrier permeability and its mechanism

作　　者：余樱[1] 张兆辉[1] 杨波[1] 曾庆杏[1] 

机构地区：[1]武汉大学人民医院神经内科,武汉430060

出　　处：《中华急诊医学杂志》2006年第12期1109-1112,共4页Chinese Journal of Emergency Medicine

基　　金：湖北省重点科技计划项目基金资助(98IP1602)

摘　　要：目的探讨溶血磷脂酸(LPA)对血脑屏障(BBB)通透性的影响及其可能机制。方法向SD大鼠右侧基底节区立体定向注射LPA或LPA+苏拉明(L+S),用伊文思蓝(EB)作为示踪剂定量测定不同时间点BBB通透性,免疫组织化学技术检测基质金属蛋白酶9(MMP-9)表达的变化,并应用透射电镜观察BBB超微结构的改变。结果LPA脑内注射后6 h同侧基底节区BBB对EB的通透性开始增加,24 h通透性达最大。到48 h通透性渐减,与对照组相同时间点比较差异有显著性(P＜0．01)。L+S脑内注射组各时间点与LPA组相应时间点相比通透性明显下降(P＜0．05)。MMP-9免疫阳性细胞主要为血管内皮细胞,LPA脑内注射后6 h免疫阳性血管数增多,于24 h表达最多,48 h逐渐减少,L+S组各时间点与之分别相比差异具有显著性(P＜0．01)。透射电镜观察到LPA组BBB基底膜粗糙、断裂,星形胶质细胞足突明显肿胀,血管周围间隙增宽等,然而L+S组上述改变不明显。结论LPA能诱导BBB通透性的增加,其可能机制为LPA受体介导的内皮细胞高表达MMP-9,降解基底膜。Objective To explore the effect of lysophosphatidic acid （LPA） on blood-brain barrier （BBB） permeability and its possible mechanism. Methods LPA or LPA ＋ suramin （L ＋ S） were stereotaxically injected into the right caudate nucleus in SD rats in vivo . Evans blue （EB） was used to quantitatively measure the permeability of BBB at different time points. The expression of matrix metalloproteinase-9 was detected by immunohistochemistry technique. The pathological ultrastructural changes of BBB were assessed by transmission electron microscopy. Results The BBB permeability began to increase after LPA administered into ipsilateral caudate nucleus, and reached the peak at 24 h. Then the permeability of BBB gradually lowered after 48 h. In comparison with the same time points of control group, there were quite significant differences （ P 〈 0.01 ）. After L ＋ S was injected , the change of BBB permeability had differences in comparison with those of LPA group in the same time points, （ P 〈 0.05）. MMP-9 positive cells were mainly vascular endothelial cells. The numbers of MMP-9 positive blood vessels grew at 6 h in LPA group, and the expression of it reached maximum at 24 h, then the number of it decreased at 48 h, showing significant statistical differences in comparison with the L＋ S group （ P 〈 0.01 ）. It was observed microscopically that ultrastructure of BBB of the LPA group was changed sharply, such as basement membrane roughed and fragmented , astrocyte end-feet swolled markedly and perivascular space enlarged obviously. But there were no remarkable changes in BBB in L ＋ S group. Conclusion LPA can induce increase of BBB permeability and its possible mechanism is the strong expression of MMP-9 protein producted by endothelial cells through the mediation of LPA receptor, leading to degradation of basement membrane.

关 键 词：溶血磷脂酸 血脑屏障 通透性 基质金属蛋白酶9 超微结构 

分 类 号：R743.34[医药卫生—神经病学与精神病学]