中国药理学与毒理学杂志2012，Vol.26Issue(3)：305-309,5.DOI:10.3867/j.issn.1000-3002.2012.03.009
吡格列酮对脂多糖诱导星形胶质细胞诱导型一氧化氮合酶表达的抑制作用
Inhibitory effect of pioglitazone on the expression of inducible nitric oxide synthases induced by lipopolysaccharide in cultured astrocytes in rats
摘要
Abstract
OBJECTIVE To investigate whether pioglitazone(Pio) can protect cortical astrocytes from lipopolysaccharide( LPS) -induced expressions of inducible nitric oxide synthases (iNOS) and release of NO, and their mechanisms. METHODS Pioglitazone 0. 1, 1.0 or 10.0 μmol·L-1, p38 mitogen-activated protein kinase ( p38 MAPK ) inhibitor SB203580 20.0 μmol·L-1, c-Jun N-terminal protein kinase (JNK) inhibitor SP600125 20.0 μmol·L-1 or peroxisome proliferator-activated receptor γ (PPARγ) inhibitor GW9662 10.0 μmol·L-1 combined Pio 1.0 μmol·L-1 treated astrocyte ( AC) cells for 1 h before LPS 10 mg·L-1 induced astrocytes. The supernatants of astrocytes were collected and analyzed for NO generation. Western blotting and immunofluorescent technology were used to observe iNOS level in astrocytes in rats. RESULTS Compared with normal control group, expression of iNOS and the release of NO in cultured astrocytes in rats markedly increased when astrocytes were induced by LPS (P <0. 01). Pio 0. 1, 1.0 and 10.0 μmol·L-1 inhibited LPS-induced increase of iNOS expression and the release of NO in cultured astrocytes. iNOS expression decreased from 1.711 ±0.283 in LPS-treated group to 0.157 ± 0.082 in Pio10. 0 μmol·L-1 group and NO release decreased from (16.63 ±2. 25) μmol·L-1 in LPS-treated group to (6.92 ±1.30)μmol·L-1 in Pio 10.0 μmol·L-1 group (P<0.01). GW9662 10.0 μmol·L-1 reversed the effects of Pio 1.0 μmol·L-1, in which iNOS expression increased from 0.562 ± 0. 100 to 0. 847 ± 0. 088 ( P < 0. 01 ) and NO release increased from (9. 27 ± 1.23μmol·L-1 to (15.54 ±2. 30) mol ·L-1 (P<0.01). SP600125 or SB20358 significantly inhibited LPS-induced increase in iNOS expression to 0. 434 ±0. 082 or 0.434 ±0.076 and NO release to (11. 53 ± 2. 40) μmol · L-1 or (8.81 ±0. 58) μmol·L-1. CONCLUSION Pio can inhibit the expression of iNOS and production of NO induced by LPS in cultured astrocytes through the activation of PPAR-y and suppression of JNK and p38MARK signal transduction pathway activity.关键词
吡格列酮/诱导型一氧化氮合酶/一氧化氮/过氧化物酶体增殖物激活受体γ/c-Jun氨基端蛋白激酶/p38丝裂原活化蛋白激酶Key words
pioglitazone/ inducible nitric oxide synthases/ nitric oxide/ peroxisome proliferator-activated receptor γ/ c-Jun N-terminal protein kinase/ p38 mitogen-activated protein kinase分类
医药卫生引用本文复制引用
刘卓,金英,隋海娟,闫恩志,刘婉珠..吡格列酮对脂多糖诱导星形胶质细胞诱导型一氧化氮合酶表达的抑制作用[J].中国药理学与毒理学杂志,2012,26(3):305-309,5.基金项目
辽宁省教育厅创新团队项目(LT2010064) （LT2010064）
辽宁医学院青年科技启动项目(Y2010Z003) （Y2010Z003）
