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目的:通过分析糖基化终末产物(advanced glycation end products,AGEs)对骨髓间充质干细胞(mesenchymal stem cells,MSCs)增殖的影响,探讨骨髓MSCs移植在合并糖尿病的冠心病患者中疗效不佳的潜在机制。方法:应用不同浓度的AGEs-BSA(0、25、50、100、200μg/mL)分别对骨髓MSCs刺激6、12、24 h,检测骨髓MSCs增殖及活性氧物质(reactive oxygen species,ROS)累积情况;并观察AGEs对细胞信号通路P38磷酸化水平的影响。结果:AGEs可加速ROS生成,并呈剂量与时间依赖性地抑制骨髓MSCs增殖活性,该效应与AGEs诱导激活P38磷酸化水平相关;P38活性的抑制可逆转AGEs对骨髓MSCs增殖抑制的影响。结论:AGEs可能通过激活P38信号通路磷酸化,诱导骨髓MSCs中ROS蓄积,进而抑制骨髓MSCs的增殖能力,减弱了骨髓MSCs移植对于合并糖尿病的冠心病患者的疗效。
OBJECTIVE: To investigate the effect of advanced glycation end products (AGEs) on the proliferation of mesenchymal stem cells (MSCs) and to investigate the effect of bone marrow MSCs transplantation in patients with coronary heart disease complicated with diabetes mellitus The potential mechanism. Methods: The bone marrow MSCs were stimulated with 0, 25, 50, 100, 200μg / mL different concentrations of AGEs-BSA for 6, 12 and 24 hours, respectively. The proliferation and the accumulation of reactive oxygen species The effects of AGEs on phosphorylation of P38 in cell signaling pathway were observed. Results: AGEs could accelerate the generation of ROS and inhibit the proliferation of MSCs in a dose-and-time-dependent manner. This effect was related to the induction of P38 phosphorylation by AGEs. The inhibition of P38 activity could reverse the effect of AGEs on the proliferation inhibition of MSCs. CONCLUSION: AGEs may be phosphorylated by activating P38 signaling pathway, inducing ROS accumulation in bone marrow MSCs, thereby inhibiting proliferation of bone marrow MSCs and attenuating bone marrow MSCs transplantation in patients with coronary heart disease complicated with diabetes mellitus.