Lake S P, Chamberlain J, Bassett P D, London N J, Walczak K, Bell P R, James R F
Department of Surgery, University of Leicester, United Kingdom.
Diabetes. 1989 Feb;38(2):244-8. doi: 10.2337/diab.38.2.244.
A method is described in which the viability of isolated adult human islets of Langerhans can be assessed in vivo. The Rowett nude rat, made diabetic with streptozocin (STZ), has been used as the islet recipient in these studies. Although these animals are athymic and are able to accept xenogeneic grafts for prolonged periods, they are very susceptible to dehydration and infection once made diabetic. Therefore, a considerably shortened diabetes induction period was used. The basis of the study was to prepare pure adult human pancreatic islets that were cultured for 48 h. Nude rats were given 80 mg/kg i.v. STZ during islet isolation and were transplanted with 800-1000 islets under the renal capsule at 48 h. To monitor islet function, animals were bled regularly for random blood glucose measurements and were given a glucose tolerance test at day 20. The kidney containing the graft was removed on day 21 to allow histological assessment of the graft and to confirm that glucose control was due to the transplanted islets and was not secondary to reversion of the animal's own islets. Seven rats were transplanted, and five were deemed to have received viable human islets. Two rats that received islets from the same donor did not reverse their diabetes and were found by histology to have vacuolated islet structures with scant insulin-staining tissue under the kidney capsule. This method allows a definitive judgment of the ability of isolated adult human islets to reverse diabetes.
本文描述了一种可在体内评估分离出的成人朗格汉斯胰岛活力的方法。在这些研究中,已将用链脲佐菌素(STZ)诱导糖尿病的罗威特裸鼠用作胰岛受体。尽管这些动物无胸腺,能够长时间接受异种移植,但一旦患糖尿病,它们极易脱水和感染。因此,采用了大大缩短的糖尿病诱导期。该研究的基础是制备培养48小时的纯成人胰腺胰岛。在胰岛分离期间,给裸鼠静脉注射80mg/kg STZ,并在48小时时将800 - 1000个胰岛移植到肾被膜下。为监测胰岛功能,定期采集动物血液进行随机血糖测量,并在第20天进行葡萄糖耐量试验。在第21天取出含有移植物的肾脏,以便对移植物进行组织学评估,并确认血糖控制是由于移植的胰岛,而非动物自身胰岛恢复所致。共移植了7只大鼠,其中5只被认为接受了有活力的人胰岛。接受来自同一供体胰岛的2只大鼠糖尿病未逆转,组织学检查发现其肾被膜下胰岛结构有空泡化,胰岛素染色组织稀少。该方法能够明确判断分离出的成人胰岛逆转糖尿病的能力。