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    SIRT1通过β-catenin核转位调控神经干细胞增殖分化的研究

    SIRT1 regulates the proliferation and differentiation of neural stem cells through β-catenin nuclear translocation

    • 摘要: 目的 探讨沉默调节蛋白1(SIRT1)调节神经干细胞增殖分化的机制。方法 细胞实验:通过免疫荧光及Western blot技术观察SIRT1激动剂白藜芦醇(resveratrol,RSV)、抑制剂尼克酰胺(nicotianamine,NA)及siRNA-SIRT1与神经干细胞共培养(24 h)后,其对神经干细胞增殖、分化的影响以及神经细胞β-catenin核转位的变化。动物实验:成年雄性SD大鼠随机分为假手术组(Sham)、缺血/复灌组(I/R)、溶剂对照组、给药组,给药组分别注射RSV和NA,采用Western blot检测各组β-catenin核转位的变化情况。结果 在神经干细胞增殖及向神经元分化的过程中,适量的RSV发挥着促进作用,而NA则是抑制这种过程,但是两者对神经干细胞向星型胶质细胞及少突胶质细胞分化基本无影响;研究发现适量的RSV可以促进β-catenin向细胞核内转移,而SIRT1的siRNA能够逆转RSV的这种促进作用。在脑缺血/再灌注损伤后,适量的RSV可以促进β-catenin向细胞核内转移,而NA可以抑制这种作用。结论 SIRT1通过调节β-catenin的核转位来调控神经干细胞的增殖和分化。

       

      Abstract: Objective To investigate the mechanism of silencing information regulator factor 1 (SIRT1) in regulating the proliferation and differentiation of neural stem cells. Methods Cell experiments:Immunofluorescence and Western blot were used to observe the effects of SIRT1 agonist resveratrol (RSV), inhibitor Nicotianamine (NA) and sirNA-SIRT1 co-cultured with neural stem cells (24 h) on the proliferation and differentiation of neural stem cells and the changes of β-catenin nuclear translocation of neural cells.Animal experiments: adult male Sprague-Dawley (SD) rats were randomly divided into the following groups: a Sham operation (Sham) group, an ischemia/reperfusion (I/R) group, a solvent control group and treatment groups. The treatment groups were injected with RSV or NA. Furthermore, β-catenin nuclear translocation in each group was detected by Western blot. Results RSV promoted the proliferation and differentiation of neural stem cells into neurons, while NA inhibited the differentiation of neural stem cells into astrocytes and oligodendrocytes, but RSV and NA did not affect the differentiation of neural stem cells into astrocytes and oligodendrocytes.It was found that appropriate RSV promoted β-catenin to the nucleus, which was reversed by SIRT1 siRNA treatnment.After cerebral ischemia/reperfusion injury, appropriate RSV promoted β-catenin to the nucleus, which was inhibited by NA treatment. Conclusions SIRT1 regulates the proliferation and differentiation of neural stem cells by regulating the nuclear translocation of β-catenin.

       

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