TO901317对酒精致新生小鼠大脑白质内炎症反应的调节作用  

The effects of TO901317 on alcohol-induced inflammation in white matter of neonatal mouse brain

作　　者：徐培[1] 杨阳[1] 唐小童[1] 赵美娜[1] 杨振慧[1] 王颖[1] 范晓棠[1] 

机构地区：[1]第三军医大学组织胚胎学教研室,重庆400038

出　　处：《免疫学杂志》2012年第12期1024-1027,共4页Immunological Journal

基　　金：国家自然科学基金(31070927)

摘　　要：目的观察肝脏X受体非选择性激动剂TO901317对酒精致新生小鼠大脑白质内炎症反应的调节作用。方法分别采用少突胶质前体细胞标记物血小板源性生长因子受体α(PDGFR-α),星形胶质细胞标记酸性纤维胶原蛋白(glial fibrillary acidprotein,GFAP),小胶质细胞标记物(tomato-lectin),运用免疫组织化学方法检测LXR激动剂TO901317对出生后第6天(P6)酒精致小鼠大脑胼胝体处白质炎症反应的作用及少突胶质前体细胞的调节作用。结果新生小鼠(P5)酒精暴露使脑白质处PDGFR-标记的少突胶质前体细胞数量显著减少(P<0.01),而GFAP标记的星形胶质细胞数量和tomato-lectin标记的小胶质细胞数量显著增加(P<0.01),TO901317预处理导致酒精暴露新生小鼠大脑白质PDGFR-α阳性细胞数量明显高于单纯酒精注射组(P<0.01),而GFAP,tomato-lectin阳性细胞数量明显低于单纯酒精注射组(P<0.01)。结论 LXR受体激活能有效抑制大脑白质神经炎症反应,并促进少突胶质前体细胞存活。This study aimed to investigate the modulating effects of liver X receptor（LXR） agonist TO901317 on alcohol-induced inflammation in the white matter of neonatal mouse brain.Immunohistochemistry was performed to exam the inflammatory reaction and survival of oligodendrocyte precursor cells in the corpus callosum of mice with specific antibodies such as PDGFR-α for oligodendrocyte precursor cells,GFAP for astrocyte,and biotin-conjugated tomato-lectin for microglia.Alcohol exposure at postnatal day 5（P5） could decrease of PDGFR-α expression in the white matter,but increase microglia and astrocyte activation.While TO901317 pretreatment at P4 could inhibit the over-activation of microglia and astrocytes in the white matter induced by alcohol exposure,and also increased PDGFR-α expression significantly as compared to alcohol treatment group.These results indicated that LXR agonist can protect oligodendrocyte precursor cells from alcohol exposure through inhibiting over-activation of microglia and astrocytes.

关 键 词：LXR激动剂 星形胶质细胞 小胶质细胞 少突胶质前体细胞 胼胝体 

分 类 号：R392.11[医药卫生—免疫学]