一次性静脉注射高剂量链脲佐菌素建立1型糖尿病小型猪模型

Establishment of a miniature pig model of type 1 diabetes by single intravenous injection of high dose streptozotocin

目的：探讨通过一次性注射高剂量链脲佐菌素（ streptozotocin，STZ）方法建立1型糖尿病小型猪模型的可行性。方法中华实验小型猪耳缘静脉一次性注射链脲佐菌素溶液150 mg/kg，分别在给药前和给药后10 min、30 min、90 min、第1天、第2天、第3天和第7天空腹采集静脉血，动态监测空腹血糖，并利用静脉糖耐量实验和C肽释放实验对模型进行鉴定。结果给药后第1天开始，模型组空腹血糖明显升高并始终维持在16.7～20.6 mmol/L的浓度范围，达到糖尿病标准；静脉葡萄糖耐量试验和C肽释放实验结果表明，静脉注射体积分数50％的葡萄糖1 h后模型猪血糖浓度高于11.1 mmol/L，2 h后未能恢复至空腹血糖水平；而胰岛素和C肽在注入葡萄糖后基本未发生任何反应，始终保持痕量水平。结论一次性静脉注射大剂量链脲佐菌素的方法能够成功建立1型糖尿病小型猪模型。

Objective To explore the feasibility of establishing mini-pig model of type 1 diabetes by single intrave-nous injection of high dose streptozotocin .Methods Eight male Zhonghua mini-pigs （22.6 ＆#177;1.8 kg） were administrated with high-dose streptozotocin （150 mg/kg） into the ear vein .Before and 10, 30, 90 minutes, 1, 3 and 7 days after adminis-tration of streptozotocin , blood samples were obtained respectively , and used to dynamically monitor the fasting blood-glucose. C peptide and insulin levels were evaluated by IVGTT test .Results Since 24 hours after STZ administration , the fasting blood-glucose level was increased significantly compared with that of pre-administration and maintained at 16.7-20.6 mmol/L, while the C peptide and insulin levels were decreased significantly .IVGTT results showed that blood sugar levels at 1 h af-ter intravenous injection of 50%glucose were much higher than 11.1 mmol/L and failed to restore to fasting glucose levels until 2 h, insulin and c-peptide did no response after injection of glucose , always kept at a trace level .Conclusion A sin-gle high-dose streptozotocin injection can be used to establish a mini-pig model of type 1 diabetes successfully .