裸鼠糖尿病模型的建立及皮下异种胰岛移植研究

Research on the establishment of Balb/c nu/nu mouse diabete model and its subcutaneous islet xenotransplantation

目的探讨链脲左菌素(STZ)建立BALB/c nu/nu裸鼠Ⅰ型糖尿病模型的方法,及将大鼠胰岛分离纯化后移植至糖尿病裸鼠皮下,对移植后裸鼠进行疗效评价。方法选用Balb/c裸鼠分为三组:糖尿病且胰岛移植组、糖尿病胰岛未移植组和正常组;用STZ对裸鼠进行糖尿病建模,大鼠胰岛分离、纯化后移植至糖尿病裸鼠背部皮下,进行血糖、体重和HE染色考察,以糖尿病未移植组和正常组作对照。结果STZ浓度175 mg/kg时,腹腔注射裸鼠糖尿病造模成功率高,纯化的大鼠胰岛活性较好,但移植后疗效平均维持时间约5 d,移植第5 d的OGTT结果显示胰岛皮下移植组和糖尿病组血糖均较正常组高,移植3 d时HE染色显示胰岛在皮下存活,但胰岛中心部位细胞有坏死。结论本研究建立了一种免疫排斥缺陷宿主异种胰岛皮下移植治疗糖尿病的方法,为进一步探索改进胰岛移植研究提供参考。

Objective To exlore the establishment of Balb/c nu/nu mouse diabetic model and its subcutane- ous islet xenotransplantation to analyze its therapeutic effect. Methods Balb/c nu/nu mice were chosen and divided into three groups. One group for subcutaneous islets xenotransplant, anther group, diabetes without isletst transplantation, and normal group as control. STZ was used to set up nude mouse diabete model. Rat islets were isolated and purified. Then after xenotransplanted into the skin of diabete model, blood sugar, weight and HE staining were investigated. Results STZ 175 mg/kg were intraperitoneal injected to Balb/c nude mouse which could get high success rate to make diabetlic model. The activity of rat islets was good. But the time of curative effect after xenotransplant ation could only keep about 5 d. OGTT on the 5th day after xenotransplant ation showed that the blood sugar of transplantation group and diabetes group were higher than that of the normal group. The HE staining on the 3rd day showed that islets were alive in subcutaneous tissue, but part of cells in the center of islets necrotized. Conclusion The study establishes a type of subcutaneous islet xenotransplantation on immunodeficiency host, which would provide a reference for further exploration of islets transplantation.