摘要
目的：探讨胰高血糖素样肽1-受体（GLP-1R）/沉默信息调节因子1（SIRT1）信号通路参与高糖诱导大鼠嗜铬细胞瘤细胞系（PC12）细胞衰老的机制.方法：培养PC12细胞用作神经细胞模型,采用β-半乳糖苷酶染色评价PC12细胞衰老情况;免疫印迹检测SIRT1、GLP-1R表达.结果：葡萄糖能剂量依赖性诱导PC12细胞衰老,并抑制SIRT1和GLP-1的表达,且均在葡萄糖（30 mmol/L,48 h）时效果最明显.SIRT1激动剂白藜芦醇（10μmol/L）能抑制高糖促进PC12细胞衰老的作用,而SIRT1的特异性抑制剂splitomicin（10μmol/L）能阻断白藜芦醇的作用.GLP-1R的激动剂GLP-1 （10 nmol/L）能逆转高糖对SIRT1表达的抑制作用并缓解PC12细胞的衰老,而GLP-1R特异性拮抗剂exendin（9-39）则阻断了GLP-1的作用.结论：GLP-1R/SIRT1信号通路参与了高糖诱导的神经细胞衰老的作用.
Objective： To investigate the role of GLP-1R/SIRT1 pathway in high glucose induced senescence of PC12 cells.Methods： The PC12 cells were cultured tn vitro as neural cells model. The senescence of PC12 cells was evaluated by beta galactosidase staining; The expressions of SIRT1 and GLP-1R were detected by Western blotting. Results： High glucose inhibited the expression of SIRT1 and GLP-1 that accompanied the senescence of PC12 celwhich was most obvious in glucose of 30 mmol/L at the 48th hour. Resveratrol（10 #mol/L） ,the activation of SIRT1, reversed the effects of high glucose on the senescence of PC12 cells. However, the beneficial effects of resveratrol were blocked by splitomicin（10 μmol/L）. In addition, GLP-1 upregulated SIRT1 expression and inhibited the senescence of PC12 induced by high glucose, and this effect was blocked by exendin（9-39） , a specific antagonist of GLP-1 R. Conclusion： The GLP-1R/SIRT1 signaling pathway is involved in high glucose induced neural cell senescence.
出处
《解剖学杂志》
CAS
CSCD
北大核心
2016年第3期257-261,共5页
Chinese Journal of Anatomy
基金
国家自然科学基金(81102437)
