西妥昔对脂多糖诱导的小胶质细胞活化和迁移的影响  

Cetuximab Attenuates the Activation and Migration of Microglia after LPS Stimulation

作　　者：渠文生[1] 方军[1] 杨琴[1] 詹燕[2] 李在望[3] 王伟[1] 田代实[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院神经科,武汉430030 [2]襄樊市中心医院神经内科,湖北襄樊441021 [3]南京医科大学附属无锡市人民医院神经内科,江苏无锡214023

出　　处：《神经损伤与功能重建》2011年第2期84-89,共6页Neural Injury and Functional Reconstruction

基　　金：国家自然科学基金(No.30800340);国家杰出青年科学基金(No.30725019)

摘　　要：目的:研究表皮生长因子受体(EGFR)的特异性单克隆抗体西妥昔(Cetuximab)对小胶质细胞活化及迁移的影响。方法:细菌脂多糖(LPS)诱导活化原代培养的大鼠脊髓小胶质细胞,给予西妥昔干预,免疫荧光法观察小胶质细胞形态及磷酸化EGFR表达水平的变化,Transwell法检测细胞的迁移。结果:与对照组相比,LPS诱导活化的小胶质细胞体积增大、突起增多、CD11b染色增强,伴随磷酸化EGFR表达增强;西妥昔干预后,LPS诱导的小胶质细胞形态变化不明显,磷酸化EGFR表达明显抑制。LPS诱导细胞6 h内细胞相对迁移率为(165.8±13.8)%,显著高于对照组(设为100%)(P<0.01);西妥昔干预后,LPS诱导的细胞迁移率降低为(119.4±7.4)%(P<0.01);LPS对小胶质细胞没有趋化性;西妥昔对未活化小胶质细胞的迁移影响小。结论:抑制EGFR活化可减轻LPS诱导的小胶质细胞活化及迁移,西妥昔可能通过调节小胶质细胞活化对神经损伤修复起积极作用。Objective： To investigate the effects of Cetuximab,a specific monoclonal antibody for epidermal growth factor receptor（EGFR）,on the activation and migration of microglia after lipopolysaccharide（LPS） stimulation.Methods： LPS was given to induce the activation of primary cultured microglia.After being treated by Cetuximab,the morphology and expression of phosphorylated EGFR（pEGFR） of microglia were observed under fluorescent staining,and the migration of microglia was tested with Transwell Assay.Results： When compared with control group,microglia induced by LPS showed larger processes and stronger CD11b immunoreactivity,which was accompanied by an elevated expression of pEGFR.Cetuximab treatment retrieved all these changes,resulting in similar morphological characteristics as seen in the control group and a weaker immunoreactivity of pEGFR.However,6 h LPS treatment induced significant increase in chemokinetic migration of microglia [（165.8±13.8）% of control group]（P0.01）.Cetuximab significantly inhibited migration of microglia to（119.4±7.4）%（P0.01）.No obvious effect of Cetuximab on normal cultured microglia was observed.Conclusion： Cetuximab is able to attenuate the activation and migration of microglia induced by LPS,by inhibiting the EGFR pathway.The study may suggest that Cetuximab might exert a protective role through regulating microglia activation after neuronal system diseases.

关 键 词：西妥昔 表皮生长因子受体 小胶质细胞 活化 迁移 

分 类 号：R741[医药卫生—神经病学与精神病学] R741.05[医药卫生—临床医学]