CTLA4Ig基因表达对鼠皮肤移植免疫抑制作用的研究

目的　探讨静脉注射CTLA4Ig腺病毒后在大鼠体内的表达和对同种异体移植皮肤存活的影响 ,以及该载体应用的安全性 ,为该基因治疗方法在抑制器官移植排斥反应的临床应用奠定基础。方法　供体SD大鼠皮肤移植前 1周 ,用腺病毒作载体将CTLA4Ig导入Wistar大鼠体内 ,用蛋白质斑点印迹实验检测血清中CTLA4Ig的表达 ,用腺病毒荧光抗体检测腺病毒在脏器的分布。同时还观测了各脏器的病理改变及移植物生存时间。结果　CTLA4Ig腺病毒在肝、脾、心、肺、肾均有明显分布 ,但实质细胞均未见严重损伤性改变。CTLA4Ig基因能在血清中的表达高峰时间一般在 7d左右 ,移植皮肤的生存显著长于对照组 (P <0 .0 5 )。结论　从静脉注射导入的CTLA4Ig基因能在大鼠体内表达并对同种移植的排斥反应有明显的抑制作用。

Adenovirus-mediated transfer of CTLA4Ig gene results in prolonged survival of skin all ograft

Objective To study CTLA4Ig expression and its immunoinhibitory effect on skin allograft and the safety of application of CTLA4Ig adenovirus. Methods The replication defective recombinant adenovirus was injected into the recipient Wistar rat one week before skin allograft transplantation of SD rat skin allograft. The expression of CTLA4Ig in serum was detected by Dot ELISA. The survival time of the allografts was also determined. The distribution of viruses in tissues was examined with antibody to adenovirus labeled by FITC and observed by laser confocal scanning microscopy. Furthermore, pathological changes of the organs and survival time were also investigated. Results The expression of CTLA4Ig in serum could be detected in the liver, spleen, heart, lung and kidney without severe damages and reached the peak at 7 d. The skin allograft in injection group survived significantly longer than that in control ( P <0.05). Conclusion The CTLA4Ig gene transferred into recipient rats by intravenous administration could express in the organs of these rats and result in obvious inhibitory effects on rejection reaction to the allograft skin.