α-MSH基因转染的小鼠同种异体移植心脏存活期延长  

In situ transfection of α-melanocyte stimulating hormone gene into donor heart prolongs the survival of allogeneic cardiac graft in mice

作　　者：张莉[1] 韩德平[1] 张丽娟[1] 田野苹[1] 

机构地区：[1]第二军医大学免疫学教研室

出　　处：《免疫学杂志》2008年第5期563-567,共5页Immunological Journal

基　　金：上海市科委基础研究重点项目(02JC14027)

摘　　要：目的观察α-黑素细胞刺激素(α-MSH)基因原位转染供者小鼠心脏对小鼠同种异体心脏移植排斥反应的影响。方法将携带α-MSH基因和绿色荧光蛋白(GFP)基因的重组腺相关病毒(rAAV-α-MSH)和单纯携带GFP的重组腺相关病毒(rAAV-GFP)分别经主动脉灌注原位转染供者小鼠心脏,再行同种异体心脏移植,观察心脏移植物的存活时间,测定移植心脏的C-MSH表达情况,并于术后7d测定移植心脏的细胞因子及趋化因子水平。结果腺相关病毒载体能有效地将α-MSH基因导入小鼠心脏,与rAAV-GFP空载体组[(7.0±0.33)d]和PBS组[(7.0±2.23)d]相比,rAAV-α-MSH原位转染组[(16.3±2.21)d]的心脏移植物存活时间延长。术后7d,rAAV-α-MSH原位转染组心脏移植物的Th1细胞因子(IL-2、IFN-α)水平较其它两组减低,而Th2细胞因子(IL-4、IL-10)水平升高,趋化因子MCP-1、RANTES水平下降。结论携带α-MSH基因的rAAV载体经原位转染供者小鼠心脏,能促进移植心脏局部的细胞因子格局由Th1型向Th2型偏移,降低趋化因子水平,从而延长同种异基因移植心脏的存活时间。Objective To investigate the effects of in situ transfection of α-melanocyte stimulating hormone （MSH） gene into donor heart on the allograft rejection in mice. Methods The hearts from Balb/c donors were transfected in situ by rAAV carrying green fluorescent protein （GFP） and α-MSH genes （rAAV-α-MSH） or rAAV carrying GFP alone （rAAV-GFP）, and then transplanted to the allogeneic recipients （C57BL/6）. The allograft survival time was observed. The in situ expression of α-MSH in the allografts was examined at different time-points after transplantation. The levels of cytokines and chemokines in the allografts were examined at day 7 after transplantation. Results α-MSH gene could be efficiently transferred into donor heart by rAAV vector. The survival time [（16.3 ± 2.21） d] of α-MSH gene-transfected cardiac graft was prolonged compared with those transfeeted by rAAV-GFP [（7.0 ± 0.33） d] or PBS control [（7.0 ± 2.23） d]. In rAAV-α-MSH transfected cardiac graft, Thl eytokines （IL-2 and IFN-α） and ehemokines （RANTES and MCP-1） decreased, while Th2 eytokines （IL-4 and IL-10） increased at day 7 after transplantation. Conclusion Direct dehvery of rAAV-α-MSH into the allografts can facilitate the deviation from Th1 to Th2 response and reduce the expression of ehemokines so that significantly prolongs the survival of allografts.

关 键 词：Α-黑素细胞刺激素 腺相关病毒 原位转染 心脏移植 移植排斥反应 

分 类 号：R654.2[医药卫生—外科学]