發(fā)布時間：2018-07-12 21:52

  本文選題：2型糖尿病 + 西格列汀��； 參考：《山東大學(xué)》2015年碩士論文

【摘要】：背景：2型糖尿病(type 2 diabetes Mellitus, T2DM)是典型的多基因復(fù)雜性狀疾病,發(fā)病機(jī)制復(fù)雜,已成為世界主要致死因素之一。目前認(rèn)為炎癥在T2DM及其并發(fā)癥的發(fā)生發(fā)展中起重要作用。調(diào)節(jié)性T (Treg)細(xì)胞在免疫和炎癥調(diào)控中發(fā)揮關(guān)鍵作用,研究表明T2DM患者外周Treg細(xì)胞比例失衡,可能與糖尿病及其炎癥的發(fā)生發(fā)展相關(guān)。西格列汀(Sitagliptin)是一種高選擇性二肽基肽酶-4(DPP-4)抑制劑,在體內(nèi)能通過抑制DPP-4活性減少胰高血糖素樣肽1(GLP-1)和葡萄糖依賴性促胰島素多肽(GIP)的失活,延長GLP-1活性,以葡萄糖依賴的方式促進(jìn)胰島素分泌。而且,sitagliptin對糖尿病相關(guān)的免疫炎癥異常也有顯著影響。為此,本研究希望通過分析T2DM患者外周Treg細(xì)胞數(shù)量的改變,探討Treg細(xì)胞在T2DM中的變化,并揭示sitagliptin對胰島功能及Treg細(xì)胞的影響。目的：分析西格列汀對2型糖尿病患者胰腺功能以及對調(diào)節(jié)性T (Treg)細(xì)胞的作用。方法：采用自身前后對照研究,納入符合條件的2型糖尿病(T2DM)患者和糖耐量及其它相關(guān)指標(biāo)正常的健康人群各8例,測空腹血糖(FPG)、胰島素原/胰島素比值、胰高血糖素,胰島素抵抗及胰島β細(xì)胞功能指數(shù),并采用流式細(xì)胞術(shù)檢測外周血Treg細(xì)胞占外周單個核細(xì)胞(PBMC)比例；之后糖尿病患者口服西格列汀(捷諾維)100mg/日,治療4周后,再檢測上述指標(biāo)觀察其變化情況。結(jié)果：與正常人群相比,T2DM患者血糖、胰高血糖素明顯升高,胰島素原/胰島素比值增大,胰島素抵抗指數(shù)明顯升高,胰島功能下降,Treg細(xì)胞比例下降,均P0.05；2型糖尿病患者治療后較治療前血糖降低,胰高血糖素水平下降,胰島素原／胰島素比值降低,胰島功能有明顯好轉(zhuǎn),P0.05,但外周血Treg/PBMC比例無顯著性差異。結(jié)論：西格列汀可通過對胰島β、α細(xì)胞同時作用,有效控制血糖,保護(hù)胰腺功能。但是,西格列汀短期治療對2型糖尿病患者Treg細(xì)胞數(shù)量無明顯影響,對其功能有無改善尚需進(jìn)一步研究,可能炎癥調(diào)節(jié)在西格列汀治療2型糖尿病的作用中并非發(fā)揮核心作用。
[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 偽 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.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R587.1

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本文編號：2118575