MicroRNA-21转染猪源生物人工胰腺对食蟹猴糖尿病模型的疗效

Curative Effect of MicroRNA-21 Transfer Porcine Biological Artificial Pancreas for Cynomolgus Monkey Diabetic Model

目的研究MicroRNA-21 (miR-21)转染微囊化猪源生物人工胰腺提高胰岛移植后功能的效果。方法在体外miR-21转染微囊化的胰岛,腹腔注射植入4只Ⅰ型食蟹猴糖尿病模型(8~10 kg),另有1只注射未转染miR-21微囊化猪胰岛。每只移植胰岛当量10 000 IEQ/kg。移植后前3天每天测血糖1次,以后每周测血糖1次,直至血糖回升至移植前水平。微囊化胰岛组和空微囊组在移植14天后根据其血糖水平给予长效胰岛素治疗。结果 miR-21转染的微囊化胰岛植入食蟹猴腹腔,血糖维持正常超过6个月,分别为9.7、 10.7、 12.1和13.2个月,移植前食蟹猴血糖浓度为(25.63±2.89) mmol/L,移植后24 h血糖降至(9.3±1.73) mmol/L, 48 h降至正常为(4.35±0.70) mmol/L。未转染的微囊化胰岛的食蟹猴糖尿病模型血糖正常维持了6个月,移植前血糖浓度为23.5 mmol/L,移植后24 h血糖降至6.4 mmol/L, 48 h为4.3 mmol/L,至第8个月血糖回到移植前。结论 miR-21转染微囊化胰岛能提高胰岛移植后的功能。

Objective To study the effect of MicroRNA-21(mi R-21) transfer porcine biological artificial pancreas for improving the function after eislet transplantation. Methods mi R-21 was in vitro transfected into microencapsulated islets with peritoneal cavity transplantation for 4 type Ⅰ Cynomolgus Monkey diabetic model(8 to 10 kg). Another 1 monkey was transplanted microencapsulated islets without mi R-21. The islet equivalent of each monkey was 10 000 IEQ/kg. Blood glucose was detected everyday for 3 days after transplantation, then once a week until the blood glucose returned to its pre-transplantation level. microencapsulated group and Empty microcapsule group were treated with long-acting insulin 14 days after transplantation according to the blood glucose level. Results the blood glucose of Cynomolgus Monkeys that were transplanted mi R-21 microencapsulated islets maintained normally for 9.7, 10.7, 12.1 and13.2 months(more than 6 months). The blood glucose of 4 monkeys before transplantation was(25.63 ± 2.89) mmol/L, and decreased to(9.3 ± 1.73) mmol/L at 24 h after transplantation, then to(4.35 ± 0.70) mmol/L at 48 h after transplantation. The blood glucose of the other monkey that were transplanted microencapsulated islets without mi R-21 maintained normally for 6 months. The blood glucose of this monkey before transplantation was 23.5 mmol/L, and decreased to 6.4 mmol/L at 24 h after transplantation, then to 4.3 mmol/L at 48 h after transplantation, and returned to pre-transplantation level on the 8 th month. Conclusions Microencapsulated islets with mi R-21 transfection can improve the islet function after transplantation.