自发高尿酸血症小鼠模型糖代谢相关研究

发布时间：2018-04-27 14:57

本文选题：尿酸氧化酶基因敲除纯合子小鼠 + 高尿酸血症　；参考：《青岛大学》2017年硕士论文

【摘要】：目的:观察自发高尿酸血症诱导糖代谢紊乱小鼠胰岛β细胞功能的变化,探讨自发高尿酸血症诱发和加重糖代谢紊乱的发病机制。方法:选取6周龄雄性尿酸氧化酶基因敲除纯合型小鼠(KO)8只为自发高尿酸血症组和雄性尿酸氧化酶基因敲除野生型小鼠(WT)12只为对照组。两组小鼠同时予以40mg.kg-1.d-1链脲佐菌素(STZ)溶液腹腔注射,连续注射5天建立自发高尿酸血症糖代谢紊乱小鼠模型。连续腹腔注射链脲佐菌素5天后,每天观察两组小鼠的一般状态并每天监测两组小鼠体重变化;于链脲菌素注射前、链脲佐菌素注射后第7天、第10天、第28天尾静脉取血测定两组小鼠的空腹血糖(FPG)水平及血清尿酸(UA)水平;于链脲佐菌素注射第7天始应用罗氏血糖仪每天测定小鼠尾静脉随机血糖;应用酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA法)测定小鼠空腹血清胰岛素(INS)浓度;根据空腹血糖水平及血清胰岛素浓度计算两组小鼠的胰岛素抵抗指数(HOMA-IR);并对两组小鼠的胰腺组织进行病理切片及免疫组化染色,观察两组小鼠胰岛的形态及胰岛β细胞的数目。结果:1.腹腔注射链脲佐菌素前纯合型小鼠体重平均为(20.6±1.9)g明显低于野生型小鼠体重(23.3±2.0)g,(P㩳0.05),直至实验结束纯合型小鼠体重均低于野生型小鼠体重。2.注射链脲佐菌素前纯合型小鼠空腹血糖水平平均为(7.85±0.69)mmol//L与野生型小鼠空腹血糖(7.11±0.66)mmol//L比较无明显差异(P0.05),于链脲佐菌素注射第7天、第10天纯合型小鼠空腹血糖((6.36±0.73)mmol//L,(8.11±1.71)mmol//L)明显高于野生型((5.52±0.73)mmol//L,(5.45±0.47)mmol//L)(P㩳0.05)。3.注射链脲佐菌素前纯合型小鼠胰岛素浓度(82.99±15.52)m U//L明显高于野生型小鼠(50.22±12.67)m U//L(P㩳0.05)。4.自链脲佐菌素注射第7天始纯合型小鼠随机血糖水平(12.0±2.2)mmol/L明显高于野生型小鼠(9.3±1.0)mmol/L(P㩳0.05),直至实验结束纯合型小鼠随机血糖均高于野生型小鼠。5.链脲佐菌素注射前纯合型小鼠血清尿酸水平为(524.17±72.75)umol/L明显高于野生型小鼠(189.33±30.19)umol/L(P㩳0.05),注射链脲佐菌素第10天纯合型小鼠血清尿酸升高的幅度大于野生型小鼠。6.链脲佐菌素注射前纯合型小鼠胰岛素抵抗指数(1.49±0.07)明显高于野生型(1.20±0.15)(P㩳0.05)。7.两组小鼠胰腺组织免疫组化染色,尿酸氧化酶基因敲除纯合型小鼠胰岛β细胞明数目少于野生型小鼠(P㩳0.05)。结论:持续血尿酸水平升高可以导致血糖升高,诱发或加重胰岛β细胞损伤。
[Abstract]:Aim: to observe the changes of islet 尾 -cell function in mice with hyperuricemia induced by spontaneous hyperuricemia, and to explore the pathogenesis of spontaneous hyperuricemia induced and aggravated glucose metabolism disorder. Methods: a total of 8 male homozygous male uric acid oxidase gene knockout mice at 6 weeks of age were selected as the control group and 12 male hyperuricemia mice and 12 wild type male uric acid oxidase gene knockout mice as control group. Two groups of mice were injected intraperitoneally with 40mg.kg-1.d-1 streptozotocin (STZ) solution at the same time, and the model of hyperuricemia and glucose metabolism disorder was established by continuous injection for 5 days. After continuous intraperitoneal injection of streptozotocin (STZ) for 5 days, the general status of the two groups was observed daily and the body weight of the two groups was monitored daily, and before and after streptozotocin injection, the mice were observed on the 7th and 10th day after streptozotocin injection. Fasting blood glucose (FPG) level and serum uric acid (UAA) level were measured on the 28th day after intravenous injection of streptozotocin, and the random blood glucose of caudal vein of mice was measured by Roche blood glucose analyzer at the 7th day after streptozotocin injection. The fasting serum insulin (ins) concentration in mice was determined by enzyme linked immunosorbent assay-ELISA (enzyme-linked immunosorbent assay (Elisa)). According to the fasting blood glucose level and serum insulin concentration, the insulin resistance index (HOMA-IRN) of the two groups was calculated, and the pancreatic tissues of the two groups were stained with pathological sections and immunohistochemical staining to observe the shape of pancreatic islets and the number of islet 尾 cells in the two groups. The result is 1: 1. The average body weight of homozygous mice before intraperitoneal injection of streptozotocin was 20.6 卤1.9g, which was significantly lower than that of wild mice (23.3 卤2.0g / kg), and the weight of homozygous mice was lower than that of wild-type mice (0.2g) until the end of the experiment. The mean fasting blood glucose level of homozygous mice before streptozotocin injection was 7.85 卤0.69)mmol//L and that of wild type mice was 7.11 卤0.66)mmol//L respectively. There was no significant difference in fasting blood glucose levels between homozygous mice and wild type mice before streptozotocin injection. The fasting blood glucose levels of homozygous mice before streptozotocin injection were 6.36 卤0.73 mmol / r / L 8.11 卤1.71 mmol / L respectively on the 7th day and 10th day after streptozotocin injection. The insulin concentration of homozygous mice before streptozotocin injection was 82.99 卤15.52 渭 r / L, significantly higher than that of wild type mice. The random blood glucose level of homozygous mice was significantly higher than that of wild mice (9.3 卤1.0 渭 mol / L, 0.05g / L) from the 7th day after injection of streptozotocin, and up to the end of the experiment, the random blood glucose levels of homozygous mice were significantly higher than those of wild mice. The serum uric acid level of homozygous mice before streptozotocin injection was 524.17 卤72.75)umol/L significantly higher than that of wild type mice (189.33 卤30.19 渭 mol / L). The serum uric acid level of homozygous mice was higher than that of wild-type mice on the 10th day after streptozotocin injection. The insulin resistance index of homozygous mice before streptozotocin injection was 1.49 卤0.07), which was significantly higher than that of wild type (1.20 卤0.15). Immunohistochemical staining showed that the number of 尾 cells in pancreatic islets of homozygous mice was less than that of wild type mice. Conclusion: elevated serum uric acid level can lead to elevated blood glucose and induce or aggravate islet 尾-cell injury.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R589.7;R-332

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