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与IGFBP-3相关的RXRα、STAT-1信号通路在β-淀粉样肽_(1~42)诱导大鼠海马神经元凋亡中的可能作用 被引量:1

EFFECTS OF IGFBP-3/RXRα OR STAT-1 SIGNALING PATHWAY ON Aβ_(1-42) INDUCED APOPTOSIS IN RAT HIPPOCAMPUS NEURONS
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摘要 目的探讨胰岛素样生长因子结合蛋白-3(IGFBP-3)、视网膜X受体α(RXRα)及信号转导子和转录激动子(STAT-1)在β-淀粉样肽1~42(Aβ1~42)诱导大鼠海马神经元凋亡中的可能作用。方法以原代培养的大鼠海马神经元为模型,分为对照组和Aβ1~42组,加入不同浓度的凝聚态Aβ1~42,原位缺口末端标记法(TUNEL)观察凋亡细胞的形态;免疫细胞荧光方法检测凋亡细胞及IGFBP3、RXRα阳性细胞;免疫印迹法检测RXRα蛋白和STAT-1蛋白的表达水平。结果20μmol/LAβ1~42作用大鼠海马神经元24h能明显诱导神经元凋亡,表现为TUNEL/DAPI染色出现阳性细胞;20μmol/LAβ1~42作用大鼠海马神经元3~6h后IGFBP3阳性细胞、RXRα阳性细胞、RXRα蛋白的表达水平均较对照组有明显增高(P<0.01),在较高水平保持一段时间后逐渐下降;而STAT-1蛋白的表达水平则显著降低(P<0.01)。结论IGFBP3/RXRα或STAT-1信号转导通路可能在Aβ1~42诱导大鼠海马神经元凋亡中起一定作用。 Objective To investigate the effects of IGFBP-3, RXRα and STAT-1 on Aβ1-42 hippocampus neurons. Methods Apoptosis was induced by fibrillar Aβ1-42 . The percentage of neurons microscopy after staining with TUNEL/DAPI. IGFBP-3 and RXRa positive neurons were observed by induced apeptosis in rat apoptosis was evaluated by immunofluorescence. The expression of RXRa and STAT-1 protein were detected by Western blotting. Results After treatment with 20μmol/L Aβ1-42 for 24 hours, the apoptotic hippocampus neurons were shown by TUNEL/DAPI assay. The percentage of apoptotic neurons was increased in a time-dependent manner. During the development of apoptosis, both the percentage of IGFBP-3/ RXRa positive neurons and the expression of RXRa protein increased markedly after 3-6hours (P 〈 0.01). However, the expression of STAT-1 protein significantly decreased ( P 〈 0.01 ). Conclusion IGFBP-3/RXRa or STAT-1 signaling pathway may be a possible signaling pathway during Aβ1-42 induced apoptosis in rat hippocampus neurons.
出处 《解剖学报》 CAS CSCD 北大核心 2008年第6期810-815,共6页 Acta Anatomica Sinica
基金 福建省自然科学基金资助项目(C0440010)
关键词 β-淀粉样肽1-42 凋亡 胰岛素样生长因子结合蛋白-3 视网膜X受体α 信号转导子和转录激动子 海马神经元 免疫细胞荧光 免疫印迹法 大鼠 β-amyloid1-42 Apoptosis Insulin-like growth factor-binding protein-3 (IGFBP-3) Retinoid X receptor-or (RXRα) STAT-1 Hippocampus neuron Immunofluorescence Western blotting Rat
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