催乳素对胰岛β细胞凋亡的保护作用及其机理研究-生物化学与分子生物学专业论文.docxVIP

THE PROTECTIVE EFFECT OF PROLACTIN ON PANCREATIC BETA CELL APOPTOSIS AND ITS MECHANISM RESEARCH ABSTRACT Diabetes can be divided into type 1 diabetes and type 2 diabetes, which is one of the major diseases risks to human health. Autoimmune attacking, inflammatory factors and glucolipotoxicity induced pancreatic β cell apoptosis play a key role in onset and development of both diabetes types. Therefore, the study of abnormal pancreatic β cell apoptosis mechanism, and further, find ways to protect β cell apoptosis will provide important guidance for diabetes treatment. In this study, we chose in vitro cultured mouse pancreatic β cell lines as experimental material, incubated these cell lines with inflammatory cytokines IL-1β、IFNγ、and high concentration of glucose、palmitate to imitate in vivo diabetes patient environment, analyzed prolactin’s protective effect on pancreatic β cell apoptosis. We found that prolactin can significantly protect pancreatic β cell from inflammatory cytokines and high glucose and palmitate induced apoptosis, and this protective effect is related to Jak2-STAT5 signaling pathway activation. Using Jak2 specific inhibitor AG490 block Jak2 protein kinase activity could significantly inhibit the protective effect of prolactin caused by glucolipotoxicity. In addition, our study found that high concentration of high glucose and palmitate induce pancreatic β cell endoplasmic reticulum stress, while prolactin can completely rescue endoplasmic reticulum stress caused by glucolipotoxicity, which may explain its protective role of β cell apoptosis. Keywords: β cell apoptosis, Prolactin, Inflammatory factor, Glucolipotoxicity, ER stress 目 录 摘 要I ABSTRACT II 目 录 IV 第一章 研究背景 1 1.1 糖尿病的概念，分类及影响 1 1.2 胰岛Β细胞数量及血糖调控 1 1.2.1 成人体内胰岛β细胞数量的调控 2 1.2.2 β细胞数量与糖尿病的关系 3 1.3 胰岛Β细胞凋亡机理 4 1.3.1 I型糖尿病中胰岛β细胞凋亡机理 4 1.3.2 II型糖尿病中胰岛β细胞凋亡机理 6 1.4 催乳素及其生理功能 10 1.5 研究目的及意义 12 1.6 本章小结 13 第二章 材料和方法 14 2.1 仪器与试剂 14 2.1.1 细胞培养相关试剂 14 2.1.2 细胞处理相关试剂 15 2.1.3 实验相关试剂 16 2.1.4 实