糖基化终末产物抑制骨髓间充质干细胞增殖的机制研究

Mechanism of advanced glycosylation end products on inhibiting the proliferation of bone marrow mesenchymal stem cells

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 study the impact of advanced glycosylation end products （AGEs） on proliferation of bone marrow mesenchymal stem cells （MSCs） and to explore the potential mechanism of poor efficacy of MSCs transplantation in coronary artery disease （CAD） patients with diabetes mellitus. Methods： MSCs were incubated with different concentrations of AGE-BSA （0, 25, 50, 100 and 200 μg/mL） for 6,12 and 24 h. The cell proliferation and ROS （reactive oxygen species） generation in MSCs were measured,as well as the phosphorylation levels of P38 signaling pathway. Results： AGEs significantly inhibited MSCs proliferation in a dose-and time-dependent manner and induced ROS generation. In addition,the phosphorylahion levels of P38 pathway were increased by AGEs in MSCs. Inhibition of P38 activity could reverse the effect of AGEs on cell proliferation in MSCs. Conclusions： The results indicate that AGEs inhibites the proliferarion of MSCs via activation of P38 signaling pathway, which might be associated with the decreased therapeutic effects of MSCs transplantation in CAD patients with diabetes mellitus.