细胞因子Irisin缓解高糖诱导骨髓间充质干细胞凋亡的机制研究

Mechanisms of irisin attenuates cell apoptosis of bone-marrow mesenchymal stem cells in high glucose condition

  • 摘要:
      背景  高糖可诱导骨髓间充质干细胞(bone-marrow mesenchymal stem cells,BMSCs)凋亡,而细胞因子Irisin对糖毒性所致的细胞损伤具有保护作用。
      目的  探讨细胞因子Irisin对高糖环境中BMSCs凋亡的影响及其作用机制。
      方法  复苏BMSCs并将其分为对照组(Vehicle)、高糖诱导组(high glucose,HG)、Irisin干预组(HG + irisin;Irisin)和抑制剂组(HG + irisin + compound C,CC)。各组细胞培养3 d后,流式细胞术检测细胞凋亡率。Western blotting检测凋亡相关蛋白Bcl-2/Bax比值和磷酸化AMP依赖的蛋白激酶(phosphorylated AMP-activated protein kinase,p-AMPK)、AMPK的表达水平。
      结果  与Vehicle组相比,HG组BMSCs细胞凋亡率显著升高(P<0.05);Irisin可降低高糖诱导的BMSCs细胞凋亡(P<0.05),提高Bcl-2/Bax的蛋白表达比(P<0.05),同时激活AMPK。当特异性地抑制AMPK后,Irisin缓解高糖诱导BMSCs凋亡的作用明显减弱。
      结论  Irisin可通过激活AMPK缓解高糖诱导的BMSCs凋亡。

     

    Abstract:
      Background  Previous studies revealed that high glucose could induce bone-marrow mesenchymal stem cells apoptosis, and irisin attenuated cell injury resulted from glucotoxicity.
      Objective  To investigate the effects of irisin on cell apoptosis of bone-marrow mesenchymal stem cells (BMSCs) in high glucose condition.
      Methods  BMSCs were divided into Vehicle group, HG (high glucose) group, Irisin (HG plus irisin intervention) group, and CC (HG + irisin + Compound C (CC) group. After cultured for 3 days, flow cytometry was used to evaluate apoptotic rate, and Western blotting was used to investigate protein level of Bcl-2/Bax and phosphorylated AMP-activated protein kinase (p-AMPK).
      Results  Compared with the Vehicle group, apoptotic rate of HG group increased obviously (P<0.05); while Irisin intervention could reduce apoptotic rate (P<0.05), increase Bcl-2/Bax expression (P<0.05), and activate AMPK. However, when inhibiting AMPK, the effects of Irisin on inhibiting cell apoptosis were blunted (P<0.05).
      Conclusion  Irisin can inhibit cell apoptosis of BMSCs in high glucose condition via activating AMPK.

     

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