Freyse E J, Hahn von Dorsche H, Fischer U
Acta Biol Med Ger. 1982;41(12):1203-10.
Permanent diabetes was produced in 16 out of 55 dogs by partial pancreatectomy (77% of the calculated organ weight) and simultaneous infusion of 2 mg/kg streptozotocin into the superior pancreaticoduodenal artery. The animals exhibited hyperglycemia, absolute lack of endogenous B-cell function, and ketosis, but no exocrine pancreatic insufficiency. 21 animals needed up to 7 additional subsequent intravenous streptozotocin injections (15 mg/kg each at intervals of 3 days). In 18 animals the procedure failed to render them diabetic; they died mainly from toxic effects of the drug. There were severe pathohistological changes in all streptozotocin-treated animals. Besides the well known alterations of the islets of Langerhans, lymphocytic inflammations were found in numerous organs including the exocrine pancreas. In most cases they were combined with degenerative changes of the organ parenchyma, particularly in kidney and liver. These findings were not correlated to the sex of the animals, to the occurrence and severity if diabetes, to the time of survival, or to the streptozotocin dose applied. But they were obviously related to the clinical picture existing besides diabetes. It is concluded that the model of experimental diabetes presented might be useful in a carnivorous big animal species but that toxic streptozotocin effects are to be expected when the dose administered exceeds 2 mg/kg.
通过部分胰腺切除术(切除计算得出的器官重量的77%)并同时向上胰十二指肠动脉输注2毫克/千克链脲佐菌素,在55只狗中有16只产生了永久性糖尿病。这些动物出现高血糖、内源性B细胞功能完全缺失和酮症,但没有外分泌性胰腺功能不全。21只动物需要随后额外进行多达7次静脉注射链脲佐菌素(每次15毫克/千克,间隔3天)。在18只动物中,该手术未能使它们患糖尿病;它们主要死于药物的毒性作用。所有接受链脲佐菌素治疗的动物都有严重的病理组织学变化。除了众所周知的胰岛改变外,在包括外分泌胰腺在内的许多器官中都发现了淋巴细胞炎症。在大多数情况下,它们与器官实质的退行性变化同时出现,尤其是在肾脏和肝脏。这些发现与动物的性别、糖尿病的发生和严重程度、存活时间或所应用的链脲佐菌素剂量均无关联。但它们显然与糖尿病之外存在的临床症状有关。得出的结论是,所呈现的实验性糖尿病模型可能对肉食性大型动物物种有用,但当给药剂量超过2毫克/千克时,预计会出现链脲佐菌素的毒性作用。