高脂高糖饮食联合链脲佐菌素构建巴马小型猪2型糖尿病模型稳定性研究

摘要

目的：应用高脂高糖饮食联合链脲佐菌素（STZ）构建巴马小型猪2型糖尿病（T2DM ）模型，探讨STZ对巴马小型猪糖尿病成模的影响，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10只，随机分为2组：对照组5例，喂养普通饲料；糖尿病模型组5只，喂养高脂高糖饲料，上述2组共喂养10月。11月初糖尿病模型组腹腔注射STZ 100 mg/kg ，1周后重复1次；对照组腹腔注射等剂量柠檬酸-柠檬酸钠缓冲液。观察2组小型猪体质量、空腹血糖（FPG ）、空腹胰岛素（FINS ）水平，行胰腺组织病理学检查、胰岛B细胞免疫组织化学染色分析，同时计算胰岛素抵抗指数（HOM A-IR）。结果①高脂高糖饲料喂养10月后，模型组小型猪体重、FBG、FINS及 HOMA-IR高于对照组（P＜0.01）；②模型组STZ给药后（12月末试验结束时），与对照组相比，模型组的FPG进一步升高，FINS水平明显下降（P＜0.01）；③胰腺 HE及免疫组织化学染色：成模组镜下胰岛整体形态萎缩，胰岛B细胞数目明显减少。结论采用高脂高糖饮食联合腹腔多次注射STZ可以成功构建巴马小型猪2型糖尿病模型，该方法操作简单、成模率高、稳定性较好。%Objective To provide a safe and stable animal model of type 2 diabetes (T2DM ) induced by high fat/high sucrose diet and streptozotocin (STZ) ,and investigate the effects of STZ on establishing T 2DM model in Chinese Bama miniature pigs .Methods Ten healthy male Bama miniature pigs were randomly divided into control group (5 ,feeding normal diet) and diabetic group (5 ,feeding high fat and high carbohydrates );the two groups were fed for ten months .At the beginning of eleventh month ,model group was injected with streptozotocin (STZ) 100 mg/kg ,the second intraperitoneal injection of STZ 100mg/kg was 1 week later .The control group was injec-ted with the same amount of sodium citrate solution .In two groups of miniature pig ,the levels of weight ,FPG , FINS and Hcy were detected ,and the parallel pancreatic histopathological examination and pancreas islet B cell im-munohistochemical staining analysis were studied .And the insulin resistance index (HOMA-IR) was calculated . Results ①After feeding high-fat and high-sucrose for ten months ,the serum levels of FPG ,weight ,FINS and HOMA-IR increased significantly in model group compared with control group (P<0.01);②After administration of STZ ,the serum level of FPG increased significantly and the level of FINS was lower in model group compared with control group (P<0.01);③The results of pancreatic HE and immunohistochemical staining :the numbers of islet beta cell were significantly reduced in model group .Conclusion A new T2DM animal model is established by high fat/high sucrose diet and multiple intraperitoneal injection of STZ in Bama miniature pigs .The method has the advantages of simple operation ,high success rate and safety .