巴马小型猪1型糖尿病模型胰腺病理及生化指标的变化

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。

Pancreatic pathological and biochemical changes in a Bama miniature pig model of type 1 diabetes mellitus

Objective To explore the efficacy of multiply intraperitoneal injection of streptozotocin (STZ) on establishment of type 1 diabetes mellitus (T1DM) model of Bama miniature pigs. Methods Twelve healthy male Bama miniature pigs were divided into control group (n=6) and diabetic group (n=6). Diabetic group was injected intraperitoneally with 75mg/kg STZ and one week later, with 150 mg/kg STZ. The control group was injected with the equal volume of sodium citrate solution. Fasting blood glucose was monitored by Roche glucose meter. Oral glucose tolerance test(OGTT)and insulin release test (IRT) were performed at the end of the experiment. Pancreatic tissues were collected for histopathological examination and β cell immunohistochemical staining. Results ① All miniature pigs in the diabetic group were the successful T1DM models and showed the characters of polyuria, polydipsia, polyphagia and weight loss. ② Since the 13^th day after injection, fasting blood glucose of the diabetic group increased significantly and maintained at the level of (7.6-17.1) mmol/L. ③ One week after successful modeling, OGTT and IRT results indicated that the blood glucose level was higher and insulin was lower than the control group (all P<0.01). ④ The histopathological examination of pancreatic tissue pathology suggested that the numbers of pancreatic islets and β cells significantly decreased in the diabetic group. ⑤ Islet β cell immunohistochemical results suggested that the area of positive staining in the diabetic group was lower than that in the control group[(10.68±2.78)% vs (43.63±2.83)%, P<0.01]. Conclusion A new T1DM animal model is established by multiply intraperitoneal injection of STZ in Bama miniature pigs. The method has the advantages of simple operation, high success rate and safety.