自噬在袖状胃切除术治疗ZDF大鼠的机制以及EGCG对α细胞氧化应激保护作用的研究

【作者】 张琳；

【导师】 郑静；

【作者基本信息】 华东理工大学 ， 药学（专业学位）， 2018， 硕士

【摘要】 第一部分自噬在袖状胃切除术治疗2型糖尿病大鼠中的机制研究随着社会经济的发展和人们生活方式的改变,全球范围内2型糖尿病患病率呈逐年上升趋势,而肥胖与2型糖尿病的发生有紧密联系。肥胖合并2型糖尿病患者常伴有非酒精性脂肪性肝病和心脑血管等疾病,其特点是肝脏中血脂代谢异常以及甘油三酯(TG)以脂滴的形式过度积累。临床研究表明,袖状胃切除术用于治疗减重和2型糖尿病的治疗,具有操作简单、手术时间短、并发症少等特点,使其成为广泛采用的治疗减重与糖尿病的术式,然而其对于治疗2型糖尿病的机制尚不明确。近年来随着对自噬机制的深入研究,不断有证据表明,自噬在糖代谢和脂质代谢中起到重要作用,这提示了自噬对于2型糖尿病缓解的潜在机制。前期工作表明袖状胃切除术中对于2型糖尿病大鼠模型肝脏脂肪过度积累逆转、血糖下降、胰岛素抵抗改善。本研究旨在探究袖状胃切除术后大鼠肝脏自噬的变化对于降低肝脏脂质和缓解糖尿病的作用。第二部分EGCG对过氧化氢诱导的α-细胞氧化应激保护作用的研究低血糖是糖尿病患者实现稳定代谢控制的一个主要障碍,这是一个严重的临床问题。随着糖尿病的进展,胰腺细胞对抗低血糖的能力受损;然而,目前尚不清楚在低血糖条件下α-细胞功能失调的反应是否与氧化应激有相关关系。在本研究中,我们研究表没食子儿茶素没食子酸酯(EGCG)是否对H2O2诱导的氧化应激的胰腺细胞系(αTC1-6)有抗氧化能力,我们对活性氧(ROS)的产生、细胞活力、胰高血糖素分泌和细胞凋亡进行了检测。结果表明EGCG降低了 ROS的产生和细胞凋亡,同时在特定浓度范围内恢复细胞活力和胰高血糖素分泌。综上所述,EGCG能阻止αTC1-6细胞过氧化氢诱导的氧化应激,恢复胰高血糖素的分泌功能,抑制细胞凋亡。这些结果为传统的抗高血糖治疗和抗氧化治疗提供了理论基础。更多还原

【Abstract】 Part ⅠThe mechanism of autophagy in the treatment of type 2 diabetic rats with sleeve gastrectomySleeve gastrectomy(SG)for the treatment of type 2 diabetes and loss of weight,has the advantages of simple operation,short operation time and less complications,therefore it is widely used worldwide.But the mechanism for the treatment of type 2 diabetes is not clear.In recent years,with the in-depth study of autophagy,there is constant evidence that autophagy plays an important role in glucose metabolism and lipid metabolism,which suggests the potential mechanism of autophagy for the remission of type 2 diabetes.Previous work showed that in sleeve type gastrectomy,liver fat accumulation was reversed,blood sugar decreased and insulin resistance improved in type 2 diabetic rats.The aim of this study was to investigate the changes of liver autophagy after sleeve gastrectomy in rats,and the effects in the treatment of type 2 diabetes mellitus,Part ⅡEpigallocatechin Gallate(EGCG)Prevents H202-Induced Oxidative Stress in pancreatic alpha cell line.Hypoglycemia is a major barrier to achieving stable metabolic control in patients with diabetes which is a serious clinical concern.With progression of diabetes,the ability of pancreatic a-cells which respond to hypoglycemia becomes impaired;However,it is not clear whether the dysfunctional responses of a-cells during hypoglycemia are related with oxidative stress.In the present study,we investigated whether epigallocatechin-3-gallate(EGCG)has antioxidant potential on pancreatic alpha TC1-6(aTC1-6)cell lines and protect the normal function of a-cells from H2O2 induced oxidative stress.ROS production,cell viability,glucagon secretion,and cell apoptosis were assessed.EGCG reduced ROS production and cell apoptosis,while restored cell viability and glucagon secretion within a particular concentration range.Taken together,EGCG prevented aTCl-6 cells from H2O2 induced oxidative stress,these results provide rationale for combining the conventional anti-hyperglycemia therapy and antioxidant therapy in order to avert hypoglycemia in clinical treatment of diabetes.更多还原