本文選題：尿酸氧化酶基因敲除純合子小鼠 + 高尿酸血癥　； 參考：《青島大學》2017年碩士論文

【摘要】：目的:觀察自發(fā)高尿酸血癥誘導(dǎo)糖代謝紊亂小鼠胰島β細胞功能的變化,探討自發(fā)高尿酸血癥誘發(fā)和加重糖代謝紊亂的發(fā)病機制。方法:選取6周齡雄性尿酸氧化酶基因敲除純合型小鼠(KO)8只為自發(fā)高尿酸血癥組和雄性尿酸氧化酶基因敲除野生型小鼠(WT)12只為對照組。兩組小鼠同時予以40mg.kg-1.d-1鏈脲佐菌素(STZ)溶液腹腔注射,連續(xù)注射5天建立自發(fā)高尿酸血癥糖代謝紊亂小鼠模型。連續(xù)腹腔注射鏈脲佐菌素5天后,每天觀察兩組小鼠的一般狀態(tài)并每天監(jiān)測兩組小鼠體重變化;于鏈脲菌素注射前、鏈脲佐菌素注射后第7天、第10天、第28天尾靜脈取血測定兩組小鼠的空腹血糖(FPG)水平及血清尿酸(UA)水平;于鏈脲佐菌素注射第7天始應(yīng)用羅氏血糖儀每天測定小鼠尾靜脈隨機血糖;應(yīng)用酶聯(lián)免疫吸附法(enzyme linked immunosorbent assay,ELISA法)測定小鼠空腹血清胰島素(INS)濃度;根據(jù)空腹血糖水平及血清胰島素濃度計算兩組小鼠的胰島素抵抗指數(shù)(HOMA-IR);并對兩組小鼠的胰腺組織進行病理切片及免疫組化染色,觀察兩組小鼠胰島的形態(tài)及胰島β細胞的數(shù)目。結(jié)果:1.腹腔注射鏈脲佐菌素前純合型小鼠體重平均為(20.6±1.9)g明顯低于野生型小鼠體重(23.3±2.0)g,(P㩳0.05),直至實驗結(jié)束純合型小鼠體重均低于野生型小鼠體重。2.注射鏈脲佐菌素前純合型小鼠空腹血糖水平平均為(7.85±0.69)mmol//L與野生型小鼠空腹血糖(7.11±0.66)mmol//L比較無明顯差異(P0.05),于鏈脲佐菌素注射第7天、第10天純合型小鼠空腹血糖((6.36±0.73)mmol//L,(8.11±1.71)mmol//L)明顯高于野生型((5.52±0.73)mmol//L,(5.45±0.47)mmol//L)(P㩳0.05)。3.注射鏈脲佐菌素前純合型小鼠胰島素濃度(82.99±15.52)m U//L明顯高于野生型小鼠(50.22±12.67)m U//L(P㩳0.05)。4.自鏈脲佐菌素注射第7天始純合型小鼠隨機血糖水平(12.0±2.2)mmol/L明顯高于野生型小鼠(9.3±1.0)mmol/L(P㩳0.05),直至實驗結(jié)束純合型小鼠隨機血糖均高于野生型小鼠。5.鏈脲佐菌素注射前純合型小鼠血清尿酸水平為(524.17±72.75)umol/L明顯高于野生型小鼠(189.33±30.19)umol/L(P㩳0.05),注射鏈脲佐菌素第10天純合型小鼠血清尿酸升高的幅度大于野生型小鼠。6.鏈脲佐菌素注射前純合型小鼠胰島素抵抗指數(shù)(1.49±0.07)明顯高于野生型(1.20±0.15)(P㩳0.05)。7.兩組小鼠胰腺組織免疫組化染色,尿酸氧化酶基因敲除純合型小鼠胰島β細胞明數(shù)目少于野生型小鼠(P㩳0.05)。結(jié)論:持續(xù)血尿酸水平升高可以導(dǎo)致血糖升高,誘發(fā)或加重胰島β細胞損傷。
[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 鹵1.9g, which was significantly lower than that of wild mice (23.3 鹵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 鹵0.69)mmol//L and that of wild type mice was 7.11 鹵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 鹵0.73 mmol / r / L 8.11 鹵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 鹵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 鹵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 鹵72.75)umol/L significantly higher than that of wild type mice (189.33 鹵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 鹵0.07), which was significantly higher than that of wild type (1.20 鹵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.
【學位授予單位】：青島大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R589.7;R-332

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