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目的探讨腹腔多次注射链脲佐菌素(STZ)对巴马小型猪糖尿病胰腺病理学及生化指标的影响,为糖尿病相关研究提供安全稳定的动物模型。方法选用健康雄性巴马小型猪12只,分为正常对照组(n=6)和糖尿病模型组(n=6)。糖尿病模型组腹腔注射STZ,第一次腹腔注射STZ 75 mg/kg,1周后第二次腹腔注射STZ 150 mg/kg,正常对照组注射等量柠檬酸钠溶液,动态监测2组小型猪空腹血糖;实验结束后行葡萄糖耐量试验(OGTT)、胰岛素释放试验(IRT)及胰腺组织病理学检查、胰岛β细胞免疫组化染色分析。结果 1糖尿病模型组所有小型猪均造模成功,成模后均表现多尿、多饮、多食及体质量减轻“三多一少”的症状;2自链脲佐菌素给药后13 d开始,糖尿病模型组空腹血糖明显升高并稳定在(7.6~17.1)mmol/L水平;3造模成功1周后,糖尿病模型组OGTT各时点血糖水平均高于正常对照组(P<0.01),IRT各时点胰岛素水平均低于正常对照组(P<0.01);4糖尿病模型组胰腺组织病理学检查结果显示,胰岛细胞团及胰岛β细胞数目明显减少;5胰岛β细胞免疫组化结果提示,糖尿病模型组胰岛中胰岛素染色阳性面积显著低于正常对照组[(10.68±2.78)%vs(43.63±2.83)%,P<0.01]。结论采用腹腔多次注射STZ可成功构建巴马小型猪1型糖尿病(T1DM)模型,该方法操作简单、成模率高、安全性强,是比较理想的制备小型猪T1DM模型的造模方法。
Objective To investigate the effects of multiple intra-abdominal injection of streptozotocin (STZ) on the pathological and biochemical indexes of pancreatic lesions in Bama miniature pigs, and to provide a safe and stable animal model for diabetes related research. Methods Twelve healthy male Bama miniature pigs were randomly divided into normal control group (n = 6) and diabetic model group (n = 6). STZ was intraperitoneally injected into the diabetic model group, the first intraperitoneal injection of STZ 75 mg / kg and the second intraperitoneal injection of STZ 150 mg / kg after 1 week. The normal control group was injected with the same amount of sodium citrate solution, Blood glucose, glucose tolerance test (OGTT), insulin release test (IRT) and pancreatic histopathological examination, pancreatic β-cell immunohistochemical staining after the experiment. RESULTS: All the miniature pigs in the diabetic model group were successfully established. After modeling, they all showed symptoms of polyuria, polydipsia, polyphagia and weight loss, “three more and one less”. 2 The administration of streptozotocin After 13 days, the fasting blood glucose was significantly increased and stabilized at (7.6 ~ 17.1) mmol / L in diabetic model group. 3 One week after modeling, the blood glucose levels of OGTT in diabetic model group were all higher than those in normal control group P <0.01). The levels of insulin in IRT group were lower than those in normal control group (P <0.01). The pathological examination of pancreas in diabetic model group showed that the number of islet cells and islet β-cell was significantly decreased; The results of immunohistochemistry suggested that the positive area of insulin in pancreatic islets in diabetic model group was significantly lower than that in the normal control group [(10.68 ± 2.78)% vs (43.63 ± 2.83)%, P <0.01]. Conclusion The multiple injection of STZ in the abdominal cavity can successfully construct the type 1 diabetes mellitus (TDM) model of Bama miniature pigs. The method is simple, easy to mold, high safety and is an ideal method for making T1DM model.