溶血磷脂酸通过ERK1/2通道诱导在体海马星形胶质细胞增殖

Study of lysophosphatidic acid induces hippocampus astrocyte proliferation in vivo through activating ERK1/2-channel

目的探讨溶血磷脂酸(lysophosphatidic acid,LPA)对在体海马星形胶质细胞(astrocyte,AST)活化增殖的影响及其可能的作用机制。方法在立体定向仪下向大鼠海马CA1区注射50μmol LPA以及LPA和U0126混合液5μl,在不同时间点采用免疫荧光双标记法检测磷酸化ERK1/2(p-ERK1/2)和胶原纤维酸性蛋白(GFAP)含量并使用激光共聚焦扫描、三维重建观察二者空间关系。结果 LPA注射后,GFAP阳性细胞数以及p-ERK1/2显著增加(P<0.05);p-ERK1/2早期(≤7d)主要在神经元分布区域检测到,后期(≥7d)发现p-ERK1/2主要在GFAP阳性细胞中表达。注射U0126与LPA混合液的部位未能检测到p-ERK1/2,GFAP阳性细胞数目轻度增加。结论 LPA可以通过磷酸化ERK1/2诱导大鼠海马AST增殖。

Objective To investigate the effect of lysophosphatidic acid（LPA） on regulating the proliferation of vivo hippocampus astrocyte（AST） and its possible mechanis.Methods The rat was positioned on a stereotactic frame and PBS（pH=7.4） or 50μmol LPA or solution contain 50μmol LPA and U0126 in 5μl was injected into the rat hippocampal CA1 area by a needle under stereotactic guidance.Then double-labelled immunofluorescence was used to detect GFAP and p-ERK1/2 at different times.Laser confocal scanning were used to study spatial and time relationship of p-ERK1/2 and astrocytes.Results LPA stimulated the proliferation of AST.Compared with the control group,GFAP-positive cells and p-ERK1/2 increased significantly（P〈0.05） after injection of LPA.Amazingly,the early（〈7d） phosphorylation of ERK 1/2 was not expressed in astrocytes but in the area where neurons occupied.p-ERK1/2 expression in astrocytes was not detected until 14d after LPA injection.p-ERK1/2 could＇t be test.GFAP positive cells increased little but there was still a small increase after U0126 with the LPA mixture injection.Conclusion These data suggest that LPA can induced proliferation of rat hippocampus AST by phosphorylated ERK1/2 after LPA position injection.U0126 induced AST proliferation after LPA injection partially by blocking the ERK pathway,suggesting that there still be other signal transduction pathways that LPA induced proliferation of rat hippocampus AST.