吡格列酮对脂多糖诱导的星形胶质细胞炎性细胞因子释放的影响  

Effects of pioglitazone on the cultured cortical astrocytes induced by lipopolysaccharide expressions of inflammatory cytokines

作　　者：隋海娟[1] 金英[1] 潘月星[1] 刘婉珠[2] 闫恩志[1] 

机构地区：[1]辽宁医学院药理学教研室,辽宁锦州121001 [2]辽宁医学院机能实验中心,辽宁锦州121001

出　　处：《中国药理学通报》2010年第9期1226-1230,共5页Chinese Pharmacological Bulletin

基　　金：辽宁省教育厅创新团队资助项目(No LT 2010064)

摘　　要：目的研究吡格列酮对脂多糖(LPS)诱导的星形胶质细胞炎症介质释放的抑制作用及其信号传导通路。方法神经胶质酸性蛋白(glial fibrillary acid protein,GFAP)免疫荧光染色法鉴定星形胶质细胞纯度。ELISA方法检测IL-1β、IL-6和TNF-α蛋白表达量的变化。Griess法测定培养细胞上清液中一氧化氮(NO)含量。结果星形胶质细胞经GFAP免疫荧光鉴定,其阳性率可达95%以上。LPS组能明显增加星形胶质细胞分泌IL-1β、IL-6、TNF-α及NO。吡格列酮能明显抑制LPS引起的这些作用,并呈一定浓度依赖性。过氧化物酶体增殖物激活受体γ(PPARγ)的特异性阻断剂GW9662能明显对抗吡格列酮对LPS引起的IL-1β、IL-6、TNF-α及NO增加的抑制作用。与LPS组相比,JNK特异性阻断剂SP600125(5μmol·L-1)亦能有效对抗LPS诱导星形胶质细胞IL-1β、IL-6、TNF-α及NO分泌的增加;特异性iNOS抑制剂SMT可明显抑制LPS引起的NO分泌增加。结论吡格列酮能明显改善LPS诱导的大鼠皮层星形胶质细胞的损伤,这种作用可能与激活PPARγ、抑制JNK信号传导通路有关。Aim To investigate whether pioglitazone could protect cortical astrocytes from lipopolysaccharide-induced expressions of inflammatory cytokines and the mechanisms responsible for this protective effect.Methods The different kinds of culture cell were evaluated by immunocytochemically stained with GFAP.Proinflammatory cytokines IL-1β,IL-6 and TNF-α were determined by sandwich ELISA.NO generation was measured by Griess method.Results The percentage of GFAP positive cells was about 95% after astrocytes were purified by shaking.The production of IL-1β,IL-6,TNF-α and NO increased markedly when astrocytes were induced by LPS.Pioglitazone inhibited LPS-induced increase of IL-1β,IL-6,TNF-α and NO in cultured astrocytes in a concentration-dependent manner.The PPARγ receptor antagonist GW9662 did reverse the effects of pioglitazone.JNK inhibitor SP600125 significantly inhibited LPS-induced increase of IL-1β,IL-6,TNF-α and NO.iNOS inhibitor SMT significantly inhibited LPS-induced increase of NO.Conclusion Pioglitazone protects cortical astrocytes against LPS insult at least via PPARγ receptor activation and inhibiting JNK activity.

关 键 词：吡格列酮 脂多糖 星形胶质细胞 神经胶质酸性蛋白 炎性细胞因子 过氧化物酶体增殖物激活受体Γ 信号传导通路 

分 类 号：R-332[医药卫生] R322.81