SDF-1α改善高糖对骨髓间充质干细胞存活及迁移能力的抑制作用与分子机制的研究

SDF-1α attenuates the inhibitory effect of high-glucose on rat mesenchymal stem cells survival and migration and the underlying molecular mechanisms

目的:探讨基质细胞衍生因子-1α(SDF-1α)对高糖环境(25 mmol/L)下大鼠骨髓间充质干细胞(r MSCs)存活及迁移能力的影响及相关分子机制.方法:采用全髓贴壁法纯化培养r MSCs,通过MTT法检测细胞增殖率、Hoechst 33258染色从形态学角度观察细胞凋亡评估SDF-1α对高糖环境下r MSCs存活的影响,同时通过transwell实验评估SDF-1α对高糖环境下r MSCs细胞迁移能力的影响.结果:实验结果发现,与低糖培养液(5.6mmol/L)比较,高糖培养液可明显抑制r MSCs增殖、促进细胞凋亡(P<0.05),SDF-1α(50 ng/m L)可减轻高糖培养液对细胞增殖的抑制及诱导细胞凋亡的作用(P<0.05),CXCR4受体特异性拮抗剂AMD3100(10μg/m L)虽能进一步抑制细胞增殖、诱导细胞凋亡,但差异无显著性(P>0.05).Transwell实验发现高糖培养液可明显抑制r MSCs的迁移作用(P<0.05),SDF-1α(50 ng/m L)可逆转高糖培养液对细胞迁移的抑制作用(P<0.05),AMD3100(10μg/m L)可进一步抑制细胞迁移,且差异有显著性(P<0.05).结论:SDF-1α可能通过CXCR4受体改善高糖对骨髓间充质干细胞迁移能力的抑制,而其改善高糖对骨髓间充质干细胞存活的抑制则可能通过非CXCR4受体介导,为改善MSCs用于治疗冠心病合并糖代谢异常患者心梗后心力衰竭疗效进一步提供理论依据.

Aim：To explore the influence of SDF-1αon the inhibitory effect of high-glucose （25 mmol/L）to rat mesenchymal stem cells survival and migration.Methods：The survival of MSCs in dif-ferent groups was examined by MTT assay for proliferation and Hoechst 33258 staining for apoptosis.The migration of MSCs in different groups was assessed by Transwell assay.Results：Compared with low-glu-cose （5.6mmol /L）,high-glucose inhibits rat mesenchymal stem cells survival and migration （P 0.05）,SDF-1αcan attenuate such inhibitory effects （vs high-glucose,P 〈0.05）.＆nbsp;Conclusion：SDF-1αattenuates the inhibitory effect of high-glucose on rat mesenchymal stem cell migra-tion via CXCR4 receptor,while it may attenuate the inhibitory effect of high-glucose on rat mesenchymal stem cells survival via binding to non-CXCR4 receptor.