牛磺酸对内质网应激介导的胰岛β细胞凋亡的影响

发布时间：2018-02-25 06:15

本文关键词： 2型糖尿病牛磺酸内质网应激 β细胞凋亡　出处：《沈阳农业大学》2016年硕士论文　论文类型：学位论文

【摘要】：目的：不良的饮食习惯,尤其高脂高糖饮食的大量摄入是胰岛素抵抗及胰岛β细胞功能障碍发生继而引发2型糖尿病发病的主要原因。其中胰岛β细胞凋亡是其发生发展的关键环节。内质网应激是启动β细胞凋亡发生的主要途径。牛磺酸是机体中重要的游离氨基酸,具有多种生物学功能。研究表明牛磺酸能够降低糖尿病模型大鼠血糖、抑制胰岛β细胞凋亡,但其具体机制尚不完全明确。本试验将通过长时间饲喂高脂高糖饮食联合链脲佐菌素(STZ)建立大鼠2型糖尿病模型,并从内质网应激介导的β细胞凋亡角度考察牛磺酸对2型糖尿病防治作用,为应用牛磺酸防治人类及宠物糖尿病提供理论依据。方法：购买50只SD雄性大鼠,随机分为3组,分别是空白对照组、食用高脂高糖饲料正常饮水组、食用高脂高糖饲料牛磺酸饮水组。第8周将食用高脂高糖饲料正常饮水组、食用高脂高糖饲料牛磺酸饮水组分为两部分。对一部分注射30 mg/kg STZ损伤部分胰岛β细胞继而引发2型糖尿病。以两周后空腹血糖大于7.8 mmol/L和糖耐量2 h后介于11.0-32.0 mmol/L者确定为2型糖尿病成模大鼠。继续喂养8周后检测各组大鼠血清中胰岛素、总胆固醇、甘油三酯、低密度脂蛋白、高密度脂蛋白含量及大鼠胰岛素敏感性、胰岛细胞分泌能力及胰岛素抵抗水平。采集胰尾部组织通过原位末端标记法(TUNEL)检测胰岛细胞凋亡情况,并检测内质网应激因子IRE1、XBP1和细胞凋亡因子CHOP、Caspase-12的表达量。探究牛磺酸对STZ联合高脂高糖饲料所致内质网应激β细胞凋亡的影响。结果：1)通过2型糖尿病判定方法结果证明STZ(30 mg/kg)联合高脂高糖饲料诱导大鼠2型糖尿病模型成立。2)STZ联合高脂高糖饲料诱导的2型糖尿病模型组大鼠和连续16周饲喂高脂高糖饲料组大鼠的空腹血糖、胰岛素抵抗指数、血清中胰岛素、总胆固醇、甘油三酯、低密度脂蛋白水平与对照组大鼠相比明显升高(P0.05),胰岛素敏感指数降低,胰岛素分泌指数、高密度脂蛋白含量明显降低(P0.05),在此处理基础上分别饮用牛磺酸的两组大鼠与相对应的未饮用牛磺酸两组相比空腹血糖、胰岛素抵抗指数、血清中胰岛素、总胆固醇、甘油三酯、低密度脂蛋白水平明显降低(P0.05),胰岛素敏感指数升高,胰岛素分泌指、高密度脂蛋白水平明显升高(P0.05)。3)STZ联合高脂高糖饲料诱导的2型糖尿病模型组大鼠和16周连续食用高脂高糖饲料组大鼠的胰岛细胞凋亡百分比,IRE1、XBP1基因及蛋白表达量,CHOP、Caspase-12基因表达量与对照组大鼠相比明显升高(P0.05),在此处理基础上分别饮用牛磺酸的两组大鼠与相对应的未饮用牛磺酸两组相比胰岛细胞凋亡百分比、IRE1、XBP1基因及蛋白表达量,CHOP、Caspase-12的基因表达量明显降低(P0.05)。即牛磺酸能够通过调节脂代谢紊乱、提高胰岛素敏感性及缓解内质网应激介导的β细胞凋亡,延缓2型糖尿病的发生及发展。
[Abstract]:Objective: bad eating habits, In particular, high fat and high glucose intake is the main cause of insulin resistance and islet 尾 cell dysfunction, which leads to the onset of type 2 diabetes mellitus, in which the apoptosis of islet 尾 cells is the key link in the development of insulin resistance and islet 尾 cell dysfunction. Cytoplasmic reticulum stress is the main pathway to induce 尾 -cell apoptosis. Taurine is an important free amino acid in the body. Taurine has many biological functions. Studies have shown that taurine can reduce blood glucose and inhibit islet 尾 -cell apoptosis in diabetic rats. However, the specific mechanism is not completely clear. In this study, the rat model of type 2 diabetes was established by feeding high fat and high sugar diet combined with STZ for a long time. From the perspective of endoplasmic reticulum stress-mediated 尾 cell apoptosis, taurine was used to prevent and treat type 2 diabetes mellitus. Methods: 50 male Sprague-Dawley rats were purchased and randomly divided into 3 groups. They were blank control group, normal drinking water group with high fat and high sugar diet, taurine drinking water group with high fat and high sugar feed, and normal drinking water group with high fat and high sugar diet at 8 weeks. The drinking water group of high fat and high sugar diet taurine was divided into two parts. Partial injection of 30 mg/kg STZ damaged some islet 尾 cells and induced type 2 diabetes mellitus. After two weeks, fasting blood glucose was greater than 7.8 mmol/L and glucose tolerance was between 11.0-32.0 after 2 hours. The mmol/L patients were identified as type 2 diabetic rats. After 8 weeks of continuous feeding, the serum insulin levels of the rats in each group were measured. Total cholesterol, triglyceride, low density lipoprotein, high density lipoprotein content and insulin sensitivity in rats, The pancreatic tail tissue was collected to detect the apoptosis of islet cells by Tunel in situ. The expression of endoplasmic reticulum stress factor IRE1XBP1 and apoptosis factor CHOP-Caspase-12 were detected. The effect of taurine on endoplasmic reticulum stress 尾 cell apoptosis induced by high fat and high glucose diet was investigated. The results showed that STZ(30 mg / kg combined with high fat and high sugar diet was used to induce type 2 diabetes in rats. The rats of type 2 diabetes model induced by high fat and high glucose diet were fed with high fat and high glucose diet for 16 weeks. Insulin resistance index, serum insulin, total cholesterol, triglyceride, low density lipoprotein level were significantly increased compared with the control group, insulin sensitivity index decreased, insulin secretion index decreased. The content of high density lipoprotein (HDL) significantly decreased P0.05N. On the basis of this treatment, the fasting blood glucose, insulin resistance index, serum insulin, total cholesterol, triglyceride were compared between the two groups of rats drinking taurine. Low density lipoprotein (LDL) level decreased P0.05, insulin sensitivity index increased, insulin secretion finger, High density lipoprotein level significantly increased the percentage of islet cell apoptosis in type 2 diabetic model rats induced by high fat and high glucose diet combined with high fat and high glucose diet and the percentage of apoptosis of islet cells in rats fed with high fat and high glucose diet for 16 weeks. The expression of IRE1, XBP1 gene and protein in rats with type 2 diabetes mellitus model group and rats fed with high fat and high sugar diet diet for 16 weeks were compared with that of CHOPN Caspase-12. The gene expression level was significantly higher than that in the control group (P 0.05). On the basis of this treatment, the apoptotic percentage of islet cells of the two groups of rats drinking taurine was higher than that of the control group. The expression of IRE1XBP1 gene and protein was higher than that of the control group. The expression of Caspase-12 in CHOPN was significantly lower than that of P0.05. that is, taurine could regulate lipid metabolism disorder. To improve insulin sensitivity and alleviate endoplasmic reticulum stress-mediated 尾-cell apoptosis and delay the occurrence and development of type 2 diabetes mellitus.
【学位授予单位】：沈阳农业大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R587.1

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