CTLA4Ig基因和CD40Ig基因转染供肾对异种大鼠移植肾存活的影响

目的 探讨细胞毒性T淋巴细胞相关抗原4融合蛋白(CTLA4Ig)基因和CD40Ig基因转染供肾对异种大鼠移植肾存活的影响.方法 以PcDNA3.1质粒为载体,通过脂质体2000将CTLA4Ig基因和CD40Ig基因转染豚鼠肾脏,再移植(异位肾移植)给SD大鼠.实验分4组进行:第1组供肾以PcDNA3.1空载体脂质体复合物转染(空载体组)；第2组供肾转染CD40Ig基因(CD40Ig转染组)；第3组供肾转染CTLA4Ig基因(CTLA4Ig转染组)；第4组供肾同时转染CTLA4Ig基因和CD40Ig基因(双基因转染组).术后观察各组血清肌酐、移植肾组织病理改变以及移植肾存活时间.结果 空载体组、CD40Ig转染组、CTLA4Ig转染组和双基因转染组受者的存活时间分别为(6.8±1.9)d、(40.7±10.9)d、(49.3±9.5)d和(75.7±8.0)d,3个转染组明显长于空载体组(P＜0.01),其中双基因转染组移植肾存活时间最长,与其他3组比较,差异均有统计学意义(P＜0.01).各组术后血清肌酐水平呈上升趋势,但升高幅度以双基因转染组为最低(P＜0.01).术后第30天,CD40Ig转染组和CTLA4Ig转染组存活大鼠的移植肾组织中可见大量淋巴细胞浸润,而双基因转染组的移植肾组织中仅见少量淋巴细胞浸润.结论 供肾局部同时转染CTLA4Ig基因和CD40Ig基因可明显延长其异种移植后的存活时间.

Influence of CTLA4Ig and CD40Ig gene local co-transfection on the survival of xenogenic renal allografts

Objective To observe the efficacy of CTLA4Ig and CD40Ig gene local cotransfection on the survival of renal allografts.Methods The kidneys of guinea pig were transfected with PcDNA 3.1+-CTLA4Ig and/or PcDNA 3.1+ -CD40Ig gene by Lipo2000,and the transfected kidneys were transplanted to SD rats.The recipients were divided into group 1 (transfected with PcDNA 3.1 +,mock group),group 2 (transfected with PcDNA 3.1 + -CD40Ig,CD40Ig group),group 3 (transfected with PcDNA3.1+ -CTLA4Ig,CTLA4Ig group) and group 4 (co-transfected with PcDNA 3.1+-CD40Ig and CTLA4Ig,CTLA4Ig+ CD40Ig group).The effects of CTLA4Ig and CD40Ig transfection were determined by Western blotting.The serum creatinine (Scr) in the recipients,the pathological changes of the allografts and the survival of renal allografts were observed.Results Significantly prolonged allografts survival time was observed in group 2 (40.7 ± 10.9 days),group 3 (49.3 ± 9.5 days) and group 4 (75.7 ± 8.0 days) as compared with group 1 (6.8 ± 1.9days),especially allografts got the longest survival time in group 4 (75.7± 8.0 days).The serum creatinine level was reduced in group 4 at 30th day as compared with that in group 2 and group 3.The lymphocytes infiltrating rate in the grafts was lowest in group 4 after transplantation.Conclusion Local co-transfection of CTLA4Ig and CD40Ig genes can prolong the survival time of renal allografts significantly.