GLP-1类似物联合CB-SCs教育治疗在1型糖尿病小鼠中的疗效及机制研究

脐血多能干细胞（CB-SCs）通过细胞相互接触及分泌可溶性细胞因子发挥免疫调节作用，可针对1型糖尿病（T1DM）的发病机制起治疗作用。近年来研究发现新型降糖药物GLP-1类似物也具有免疫调节效应，产生保护胰岛β细胞的作用。我们的初步临床研究显示GLP-1类似物联合CB-SCs教育治疗患者的胰岛素分泌增加，提示两者联合治疗可能具有促进胰岛β细胞增殖的作用，但具体疗效和机制尚未明了。我们推测利拉鲁肽联合CB-SCs教育治疗可降低或阻断抗原提呈细胞的免疫激活功能，抑制CD4+/CD8+ T细胞的活化，诱导免疫耐受，促进胰岛β细胞增殖再生和抑制凋亡，达到治疗T1DM的目的。本研究拟从：利拉鲁肽联合CB-SCs教育治疗T1DM模型NOD小鼠的试验，研究两者联合治疗的潜能、对胰岛β细胞的影响以及相关免疫调节和分子机制。旨在为治疗T1DM提供新的有效治疗策略。

Cord blood-derived multipotent stem cells (CB-SCs) can modulate immune cells through cell to cell contact and soluble factors, which may be a novel therapeutic method for type 1 diabetes mellitus (T1DM) against pathogenesis. Recent studies showed novel antidiabetic agents-GLP-1 analogue also have immunomodulatory effects, can protect the islet β cells. Our preliminary clinical studies have shown that insulin increased after the therapy of GLP-1 analogue with CB-SCs educator in patients with T1DM, suggesting that the combination therapy may promote islet β cell proliferation, but the specific effect and mechanism remains unclear. We speculate that the combination therapy can reduce or block the activation of antigen-presenting cells immune function, inhibit CD4+ / CD8+ T cell activation, induce immune tolerance, promote islet β cell proliferation and protect them from apoptosis, consequently achieving the purpose of treatment of T1DM. Thus, we treated NOD mouse by GLP-1 analogue with CB-SCs educator in our study, observe the potential effect of the combination therapy for NOD mouse and their islet β cells, explore the immunoregulatory and molecular mechanisms invovled in the effect of combination therapy. The aim of our study is to provide novel and effective therapeutic strategies for T1DM.