链脲佐菌素对1型糖尿病小型猪肝肾功能的影响  

Streptozocin affects the hepatorenal function of type 1 diabetes mini-pigs

作　　者：田忠[1] 崔永春[1] 李凯[1] 李巨波[1] 王坤[1] 唐跃[1] 

机构地区：[1]中国医学科学院,北京协和医学院,国家心血管病中心,阜外心血管病医院,心血管疾病国家重点实验室,北京市100037

出　　处：《中国组织工程研究》2013年第18期3366-3373,共8页Chinese Journal of Tissue Engineering Research

基　　金：实验部分内容获北京市科委科技计划“常见心脑血管缺血性疾病模型研发公共平台建设”(课题编号Z101107052210004)基金;协和青年基金“糖尿病小型猪急性心肌缺血代谢组学研究”(课题编号2012-XHQN04)资助~~

摘　　要：背景:高剂量链脲佐菌素建立小型猪1型糖尿病模型是目前国内外公认的方法,但其对实验动物肝肾功能有何影响?目的:观察高剂量链脲佐菌素建立小型猪1型糖尿病模型对其肝肾功能的影响。方法:将巴马小型猪随机分为对照组和模型组。分别在耳缘静脉注射柠檬酸钠溶液或链脲佐菌素溶液前、后10min,30min,1h,2h,4h,1d,3d和7d各静脉采血1次,动态监测空腹血糖、C肽和胰岛素水平,检查肝肾功能,通过westernblot法检测猪胰腺、肝脏、肾脏葡萄糖转运蛋白2的表达水平。结果与结论:给药后24h开始,模型组空腹血糖明显升高并始终维持在17.7-20.1mmol/L的浓度范围,C肽和胰岛素水平显著降低。与给药前相比,模型组肝肾功能血液指标中总蛋白、丙氨酸氨基转移酶、天门冬氨酸氨基转移酶和肌酐均无明显改变;尿素氮和白蛋白虽略有降低,但尚未达到显著性水平;血尿酸水平明显降低(P<0.05)。Westernblot结果表明,与对照组比较,模型组胰腺、肝和肾小管基底膜细胞葡萄糖转运蛋白2的表达均显著减少。证实,一次性注射高剂量链脲佐菌素可成功建立1型糖尿病小型猪模型,且对模型猪的肝肾功能无显著影响。BACKGROUND： It is an acknowledged method to establish type 1 diabetes models in mini-pigs with high doses of streptozocin, but there are few reports about its influence on hepatorenal function of animals. OBJECTIVE： To explore the effect of high-dose streptozocin on hepatorenal function in type 1 diabetes mini-pigs.METHODS： Obama mini-pigs were randomly divided into control group and model group. Before and 10 and 30 minutes, 1,2 and 4 hours, 1, 3 and 7 days after ear vein administration of sodium citrate or streptozocin, the blood samples were obtained respectively, and used to dynamically monitor the fasting blood-glucose, C peptide and insulin levels, and the hepatorenal function was examined. Glucose transporter protein 2 expression levels in pancreas, liver and kidney were determined by Western blot. RESULTS AND CONCLUSION： Since 24 hours after administration, fasting blood-glucose was increased significantly in the model group and maintained at 17.7-20.1 mmol/L, while the C peptide and insulin levels were decreased significantly. Compared with pre-administration, the total protein, alanine aminotransferase, aspartic acid transaminase and creatinine levels were not changed significantly in the model group; urea nitrogen and albumin levels were slightly decreased, but did not reach significant difference level; the blood uric acid was significantly reduced （P 〈 0.05）. Western blot results showed that the expressions of glucose transporter-2 of pancreas, liver and renal basilar membrane cells in the model group were significantly lower than those in the control group. One-time high-dose streptozocin injection can establish the mini-pig model of type 1 diabetes successfully, and has no significant influence on the hepatorenal function.

关 键 词：器官移植 器官移植基础实验 糖尿病 1型糖尿病 葡萄糖转运蛋白2 小型猪 肝肾功能 省级基金 

分 类 号：R318[医药卫生—生物医学工程]