中国药理学与毒理学杂志2011，Vol.25Issue(1)：34-39,6.DOI:10.3867/j.issn.1000-3002.2011.01.007
吡格列酮对淀粉样β蛋白片段25-35致大脑皮质神经元损伤的保护作用
Protective effects of pioglitazone on cultured cortical neurons injury induced by amyloid beta-protein fragment 25-35
摘要
Abstract
OBJECTIVE To investigate whether pioglitazone (Pio) can protect cortical neurons from amyloid beta-protein fragment 25 - 35 ( Aβ25-35 )-induced neurotoxicity. METHODS The cultured cortical neurons were incubated with Pio 0.01, 0.1, 1 and 10 μmol· L-1 for 1 h, then Aβ25-35 20 μmol·L-1 was added for 24 h. GW9662 was added 30 min before Pio 1 μmol·L-1 added.The cell viability was assessed by MTT assay. The neuronal apoptosis was quantified by scoring cells percentage with apoptotic nuclear morphology after Hoechst33258 staining. The protein expressions of phosphorylated mitogen-activated protein kinase kinase 4 (P-MKK4), phosphorylated c-Jun N-terminal kinase 1 (P-JNK 1 ), and Bcl-2 were measured by Western blotting. RESULTS The decrease of cell viability and increase of apoptotic cells of cultured cortical neurons were observed in Aβ25-35 group compared with normal control group. The cell viability of cortical neurons was decreased to (66.8±1.2)％ in Aβ25-35 model group (P＜0.01). Pio 0. 1, 1 and 10 μmol·L-1 could antagonize Aβ25-35 induced decreasing in cell viability in a concentration-dependent manner by (81.2 ±2.9)％,(87.9 ± 2. 2) ％ and (98. 1 ± 1.9) ％, respectively. GW9662 did partly inhibit effects of Pio on cell viability. Aβ25-35 induced increase in apoptotic cell percentage from (11.8 ± 1.1 )％ in normal control group to (64.6± 2.3 ) ％ (P ＜ 0.01 ). Pio 0. 1, 1 and 10 μmol· L- 1 prevented the increase in apoptotic cells percentage by (58.3 ±1.2)％, (52.6 ±1.3)％ and (41.5 ±1.5)％, respectively. Furthermore,neurons incubation with Aβ25-35 for 24 h induced the decrease in Bcl-2 expression, but the increase in P-MKK4 and P-JNK1 expressions. Pretreatment with Pio significantly inhibited reduction of Bcl-2 expression induced by Aβ25-35. Pio 0. 1, 1 and 10 μmol·L-1 also inhibited Aβ25-35 induced increase in MKK4 and JNK1 phosphorylation. CONCLUSION Pio protects cortical neurons against Aβ25-35 insult through PPARγ receptor activation and up-regulating Bcl-2 expression and inhibiting MKK4/JNK pathway.关键词
吡格列酮/淀粉样β蛋白片段/阿尔茨海默病/细胞凋亡/c-Jun氨基端激酶分类
医药卫生引用本文复制引用
金英,张智娟,刘婉珠,隋海娟,刘卓,王蕊,闫恩志..吡格列酮对淀粉样β蛋白片段25-35致大脑皮质神经元损伤的保护作用[J].中国药理学与毒理学杂志,2011,25(1):34-39,6.基金项目
辽宁省教育厅创新团队项目(LT2010064) （LT2010064）
辽宁省自然科学基金资助项目(20042171) （20042171）
