INF-γ在可溶性β-淀粉样蛋白(fAβ)介导的小胶质细胞神经毒性中的增敏作用  

The enhanced effect of INF-γ on neuronal injury of microglia induced with fAβ

作　　者：李艳花[1] 张海飞[1] 张鑫辰[1] 张辉[1] 尉杰忠[1] 丰玲[1] 霍明章[1] 肖保国[2] 马存根[1,3] 

机构地区：[1]山西大同大学脑科学研究所,大同037009 [2]复旦大学附属华山医院神经病学研究所,上海200040 [3]山西中医学院第三中医院脑病科,太原030024

出　　处：《复旦学报（医学版）》2013年第3期259-264,共6页Fudan University Journal of Medical Sciences

基　　金：国家自然科学基金项目(81070957);山西省青年自然科学基金项目(2012021034-2);山西大同大学博士科研启动经费项目(2011-B-11);大同大学研究所科研项目~~

摘　　要：目的通过体外实验的方法研究炎性环境促进异常聚集的可溶性β-淀粉样蛋白(fibrillarβ-amyloid,fAβ)1-42引发神经毒性的分子机制。方法使用INF-γ(100U/mL)或/和fAβ1-42(50μg/mL)剌激BV2小胶质细胞系,检测其膜式受体表达和炎性分子释放;并通过小胶质细胞和PC12神经元共培养体系,检测PC12细胞死亡和线粒体膜电位变化。结果 INF-γ诱导BV2细胞表面Aβ受体FPR2、RAGE和CD36表达明显增加。在INF-γ刺激下,fAβ1-42诱导小胶质细胞释放更多的炎性因子。在BV2和PC12共培养体系中,INF-γ和fAβ1-42的协同作用促使更多的PC12细胞走向死亡,使PC12细胞线粒体膜电位发生更强变化。结论 INF-γ诱导的Aβ结合受体表达量上调,可能参与Aβ激活小胶质细胞的炎性反应和随后的神经元毒性,可能成为今后阿尔茨海默病(Alzheimer′s disase,AD)患者治疗的靶点。Objective To explore the effect of INF-γ stimulation on fibrillar β-amyloid 1-42 （fAβ1-42） triggered neuronal injury in vitro. Methods Microglia cell line BV2 was exposed to fibrillar soluble Aβ1- 42 （50μg/mL） alone and in combination with cytokines INF-γ （100 U/mL）. The expression of Aβ membrane receptors mRNA and the release of inflammatory cytokines were detected. Mitochondrial membrane potential cell death was analyzed by flow cytometry under BV2 and PC12 co-culture system. Results INF-γ treatment significantly enhanced the mRNA level of CD36,FPR2 and RAGE in BV2 cells. INF- y and fAβ1-42 synergistically increased the production of proinflammatory cytokines IL-1β, TNF-α and NO. Under the co-culture system of BV2 and PC12,INF-α and fAβ-42 synergistically increased more cell death and decreased mitochondrial membrane potential in PC12 cells. Conclusions Our findings indicate that INF-γ profoundly increases microglial inflammatory responses to Aβ peptide and neurotoxic effects possible through inducing membrane receptors that can bind Aβ peptide and may be an approach for treating AD in humans.

关 键 词：阿尔茨海默病(AD) 小胶质细胞 神经元 BETA-AMYLOID INF-Γ 

分 类 号：R749.16[医药卫生—神经病学与精神病学]