CTLA4Ig基因对大鼠胰岛移植后排斥反应的治疗作用

目的　研究CTLA4Ig基因在糖尿病大鼠体内表达及其产物对胰岛移植物存活的作用。方法　利用Lipofectin载体包裹CTLA4IgcDNA质粒后转染鼠胰岛和肌肉细胞 ,检测移植后CT LA4Ig表达和T淋巴细胞转化率。结果　胰岛移植术后 7dT淋巴细胞转化试验 ,实验组 (A组 )和对照组 (B组 )每分钟脉冲数 (cpm)分别为175 .7± 98.2 ,2 5 4.4± 116 .3 ,两组比较差异显著 (P <0 .0 5 )。A组胰岛移植第 7d ,2只大鼠血清CTLA4Ig呈阳性 (阳性率 2 0 % )。A、B两组胰岛移植后血糖维持正常时间分别为 (14.8± 12 .3)d和 (3 .6± 5 .1)d ,两组比较差异显著 (P <0 .0 5 )。A、B两组大鼠平均存活时间分别为 (2 4.0± 10 .8)d和 (10 .8± 4.8)d ,两组比较 ,差异有极显著性 (P <0 .0 1)。结论　脂质体包裹的CTLA4IgcDNA转染肌细胞和胰岛细胞 ,可以在受体大鼠胰岛细胞或肌肉组织中表达 ,其表达产物可使胰岛移植物和受体鼠存活时间明显延长 ,抑制细胞免疫活性 ,发挥其治疗排斥反应的作用

Treatment of CTLA4Ig gene for the rejection of pancreatic islet allograft in diabetic rats

Objectives To study the expression of CTLA4Ig gene in diabetic rat and the action of CTLA4Ig on prolonging survival time of the pancreatic islet.Methods The rat pancreatic islet cells and muscle cells were transfected with the cDNA for CTLA4Ig packaged with lipofectin vector.The expression levels of CTLA4Ig gene and T lymphocyte reaction(MLR)were determined and the action of CTLA4IgcDNA on prolonging survival time of the pancreatic islet allograft in diabetic rats observed.Results T lymphocyte transforming test from peripheral intravenous blood at 7 th day after pancreatic islet transplantationrevealed that cpm in group A and group B were 175.7±98.2,254.4±116.3,respectively,with the difference between the two groups being significant(P＜0.05).At 7th day after pancreatic islet allograft in group A,only 2 out of 10 recipients were serum CTLA4Ig positive with their concentrations being 14 ng/ml and 31 ng/ml respectively. The average time of maintaining blood glucose normal levels in the group A after pancreatic islet allograft,(14.8±12.3)days,was significantly longer than (3.6±5.1)days of the roup B(P＜0.05),The average survival time in the group A.(24.0±10.8)days (the longest time was 45 days), was significantly longer than(11.8±4.8)days(the longest time was 21 days)of the group B (P＜0.01). Conclusions The muscle cells and pancreatic islets of the recipient rats were transfected with CTLA4Ig cDNA packaged with lipofectin.CTLA4Ig cDNA could be expressed in the recipient tissues. The expressed product could obviously prolong the survival time of the pancreatic islet allograft and the recipient rats and partly inhibit the cellular immunity to prevent rejection.