AICAR通过提高MSC移植存活率促进糖尿病溃疡创面愈合的研究

AICAR promotes the wound healing in diabetic ulcers by improving the survival rate of MSC in biomaterials transplantation

目的探讨AICAR通过提高间充质干细胞(MSC)在生物材料中移植存活率的机制及对糖尿病溃疡的治疗效果。方法将40只5~8周雄性C57BL/6J小鼠腹腔注射链脲佐菌素造成糖尿病小鼠模型,然后结扎股动脉,制备小鼠糖尿病足溃疡模型。实验分为对照组、MSCs组、阿卡地新(AICAR)组以及AICAR-MSCs组,每组10只。利用流式细胞实验、Transwell迁移实验观察AICAR对MSCs抗凋亡和迁移的影响,检测条件培养基中VEGF含量。制备小鼠糖尿病足溃疡模型,含AICAR刺激的MSCs覆盖创面,2周后CD31染色,分别观察创面血管新生状况。结果与空白对照组和MSCs对照组相比,细胞实验结果显示,AICAR刺激的MSCs实验组具有较低的MSCs凋亡率、良好的MSCs迁移能力和较高的VEGF分泌作用。动物实验结果显示AICAR刺激的MSCs覆盖糖尿病足溃疡创面可促进血管新生,加速溃疡愈合。结论 AICAR通过抑制高糖对MSCs的凋亡影响,促进MSCs的存活和旁分泌作用,从而促进血管新生,加速溃疡愈合。

Objective To investigate the mechanism of AICAR in improving the survival of mesenchymal stem ceUs （MSCs） in bioma- terials and the therapeutic effect on diabetic ulcer. Methods Totally 40 male C57BL/6J mice were equally divided into 4 groups：control group, MSCs group, AICAR group and AICAR-MSCs group. The effects of AICAR on the apoptosis and migration of MSCs were observed by flow cytometry and transwel｜ migration assay. The expression of VEGF in conditioned medium was detected. Prepared diabetic foot ulcer model and AICAR-stimulated MSCs-covered wounds. The wound neovascularization was observe by CD31 staining 2 weeks later. Results Compared with the control group and MSCs group, the resuhs of the cell experiments showed that the AICAR-MSCs group had lower MSCs apoptosis rate, better MSCs migration ability and higher VEGF secretion. Animal experiments showed that AICAR-stimulated MSCs covered diabetic foot ulcer wounds had good angiogenesis and rapid ulcer healing processes. Conclusion AICAR promotes the survival and paracrine effect of MSCs by inhibiting the high glucose effect on MSCs apoptosis, so as to promote the angiogenesis and accelerate the healing of ulcer.