西格列汀对2型糠尿病患者胰岛功能及调节性T细胞作用的研究

发布时间：2018-07-12 21:52

本文选题：2型糖尿病 + 西格列汀　；参考：《山东大学》2015年硕士论文

【摘要】：背景：2型糖尿病(type 2 diabetes Mellitus, T2DM)是典型的多基因复杂性状疾病,发病机制复杂,已成为世界主要致死因素之一。目前认为炎症在T2DM及其并发症的发生发展中起重要作用。调节性T (Treg)细胞在免疫和炎症调控中发挥关键作用,研究表明T2DM患者外周Treg细胞比例失衡,可能与糖尿病及其炎症的发生发展相关。西格列汀(Sitagliptin)是一种高选择性二肽基肽酶-4(DPP-4)抑制剂,在体内能通过抑制DPP-4活性减少胰高血糖素样肽1(GLP-1)和葡萄糖依赖性促胰岛素多肽(GIP)的失活,延长GLP-1活性,以葡萄糖依赖的方式促进胰岛素分泌。而且,sitagliptin对糖尿病相关的免疫炎症异常也有显著影响。为此,本研究希望通过分析T2DM患者外周Treg细胞数量的改变,探讨Treg细胞在T2DM中的变化,并揭示sitagliptin对胰岛功能及Treg细胞的影响。目的：分析西格列汀对2型糖尿病患者胰腺功能以及对调节性T (Treg)细胞的作用。方法：采用自身前后对照研究,纳入符合条件的2型糖尿病(T2DM)患者和糖耐量及其它相关指标正常的健康人群各8例,测空腹血糖(FPG)、胰岛素原/胰岛素比值、胰高血糖素,胰岛素抵抗及胰岛β细胞功能指数,并采用流式细胞术检测外周血Treg细胞占外周单个核细胞(PBMC)比例；之后糖尿病患者口服西格列汀(捷诺维)100mg/日,治疗4周后,再检测上述指标观察其变化情况。结果：与正常人群相比,T2DM患者血糖、胰高血糖素明显升高,胰岛素原/胰岛素比值增大,胰岛素抵抗指数明显升高,胰岛功能下降,Treg细胞比例下降,均P0.05；2型糖尿病患者治疗后较治疗前血糖降低,胰高血糖素水平下降,胰岛素原／胰岛素比值降低,胰岛功能有明显好转,P0.05,但外周血Treg/PBMC比例无显著性差异。结论：西格列汀可通过对胰岛β、α细胞同时作用,有效控制血糖,保护胰腺功能。但是,西格列汀短期治疗对2型糖尿病患者Treg细胞数量无明显影响,对其功能有无改善尚需进一步研究,可能炎症调节在西格列汀治疗2型糖尿病的作用中并非发挥核心作用。
[Abstract]:Background type 2 diabetes Mellitus (T2DM) is a typical polygenic complex disease with complex pathogenesis and has become one of the major lethal factors in the world. It is believed that inflammation plays an important role in the occurrence and development of T 2 DM and its complications. Regulatory T (Treg) cells play a key role in the regulation of immunity and inflammation. Studies have shown that the imbalance of peripheral Treg cells in patients with T2DM may be related to the occurrence and development of diabetes mellitus and inflammation. Sitagliptin is a highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor, which can reduce the inactivation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulin stimulating peptide (GIP) and prolong the activity of GLP-1 by inhibiting the activity of DPP-4 in vivo. Promote insulin secretion in a glucose-dependent manner. And sitagliptin also has a significant effect on diabetes-related immune inflammation abnormalities. Therefore, the purpose of this study was to explore the changes of Treg cells in T2DM by analyzing the changes of peripheral Treg cells in patients with T2DM, and to reveal the effects of sitagliptin on islet function and Treg cells. Aim: to investigate the effects of siglitatin on pancreatic function and regulatory T (Treg) cells in patients with type 2 diabetes. Methods: fasting blood glucose (FPG), proinsulin / insulin ratio and glucagon were measured in 8 patients with type 2 diabetes mellitus (T2DM) and 8 healthy subjects with normal glucose tolerance and other related parameters. Insulin resistance and islet 尾 cell function index were measured by flow cytometry, and the percentage of peripheral blood Treg cells in peripheral blood mononuclear cells (PBMCs) was measured by flow cytometry. The changes of the above indexes were observed. Results: compared with the normal group, the blood glucose, glucagon, proinsulin / insulin ratio, insulin resistance index and islet function decreased significantly (P 0.05) in the patients with T2DM. After treatment, the blood glucose decreased, the glucagon level decreased, the proinsulin / insulin ratio decreased, and the pancreatic islet function improved significantly (P0.05), but there was no significant difference in the ratio of Treg-PBMC in peripheral blood. Conclusion: siglitatin can effectively control blood glucose and protect pancreatic function by simultaneously acting on islet 尾 and 伪 cells. However, the short-term treatment of siglitatin has no significant effect on the number of Treg cells in type 2 diabetes mellitus, and the improvement of its function still needs further study. It may be that the regulation of inflammation does not play a central role in the treatment of type 2 diabetes mellitus by siglitatin.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1

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