[目的]1型糖尿病是由于慢性免疫炎症破坏了胰岛β细胞,导致血糖升高.间充质干细胞可以预防及治疗糖尿病及其并发症的发生,然而对牙龈间充质干细胞(GMSCs)预防糖尿病的效果和潜在机制知之甚少.本研究旨在研究GMSCs在预防小鼠1型糖尿病的机制,寻找临床治疗糖尿病的靶点.[方法]我们将人GMSCs注射到NOD小鼠体内,观察血糖的变化趋势,通过免疫组化染色观察胰岛β细胞的存活情况,并通过流式分析检测小鼠脾脏中T细胞、B细胞及巨噬细胞的比例变化.最后,将NOD小鼠脾脏淋巴细胞回输至NOD-SCID小鼠,观察NOD-SCID小鼠的血糖水平及糖尿病发病率.[结果]GMSCs明显降低了NOD小鼠的糖尿病发病率,对照组小鼠在27周龄时有64%患糖尿病,而GMSC组只有35%,P=0.013.GMSCs处理的小鼠脾脏中滤泡B细胞比例从(52.2±4.1)%下降到(43.2±5.3)%,P =0.008,而其他类型的免疫细胞没有明显变化.免疫组化结果显示,GMSCs可以有效地提高胰岛β细胞的存活率,使其能够持续产生胰岛素以控制血糖.最后,我们发现患病小鼠脾脏淋巴细胞回输治疗能够促进NOD-SCID小鼠糖尿病的发生.[结论]GMSCs可以通过减少脾脏中的滤泡B细胞比例来预防NOD小鼠的糖尿病发生.
[Background]Type 1 diabetes is caused by a chronic immune response that destroys islet beta cells,re-sulting in elevated blood glucose.Mesenchymal stem cells can prevent and treat the development of diabetes and its compli-cations.However,little is known about the effects and potential mechanisms of Gingival mesenchymal stem cells(GMSCs)in preventing diabetes.The aim of this study is to investigate the mechanism of GMSCs in preventing type 1 diabetes in mice and to find targets for clinical treatment of diabetes.[Methods]We injected human GMSCs into NOD mice to observe the trend of blood glucose,observed the survival of pancreatic β-cells by immunohistochemistry,and detected the change of immune cells in the spleen of mice by flow analysis.Finally,the immune cells in NOD mice were transfused into NOD-SCID mice to observe the onset of diabetes in NOD-SCID mice.[Results]GMSCs significantly reduced the incidence of di-abetes in NOD mice,with 64%of control mice developing diabetes at 27 weeks of age compared with 35%in the GMSC group,P=0.013.The percentage of Follicular B cells(FO B cell)in the spleen of GMSCs-treated mice decreased from(52.2±4.1)%to(43.2±5.3)%,P=0.008,while other types of immune cells did not change significantly.The immunohisto-chemical results showed that GMSCs could effectively improve the survival of pancreatic β-cells,which could continuous-ly produce insulin to control blood glucose.Finally,we found the spleen cells transfusion could prevent the development of diabetes in NOD-SCID mice.[Conclusion]GMSCs can reduce diabetes in mice by reducing FO B cells in the spleen.