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Gene therapy in lung transplantation. Attenuation of ischemia/reperfusion injury and acute rejection by NF-kB decoy transfection

肺移植中的基因治疗。

基本信息

批准号：
12671307
负责人：
MINAMI Masato
金额：
$ 2.18万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671307/
关键词：
rat lung transplantation nitric oxide acute rejection NF-kB decoy transfection HVJ liposome lung injury NFKB 肺移植肺傷害 NFkB HVJ-liposome法

项目摘要

This study are to determine whether NF-kB decoy transfection into the allograft during harvest reduce nitric oxide (NO) production and ameliorate acute lung rejection. Left lung transplantation was performed using pairs of Brown Norway(RT1n) and Lewis (RT1I) rats. All allografts were flushed with PBS solution 20 ml containing hemaglutinating virus of Japan (HVJ) liposome-ODNs complex of NF-kB decoy (n=6) and preserved for 60 minutes at 4℃, Scrambled decoy was regarded as control (n=5) as well as simple PBS solution (n=5). Five days after transplantation without use of immunosuppressants, exhaled NO, gas exchange and histological rejection score of the graft were determined. Exhaled NO level significantly reduced in group with NF-kB decoy transfection compared with control (445±162 vs. 1305±123 ppb, p<0.02) as well as improvement in PaO2 (197±28 vs. 60±18 mmHg, p<0.02) and rejection score (1.6±0.4 vs. 2.5±0.4). Inhibition of NF-kB activation in the allograft by ODNs decoy transfection into the donor lung ameliorated lung injury in acute allograft rejection. This result implies a possible therapeutic target for allo-independent pathway, which seemed to be feasible in conjunction with immuinosuppression in the clinical setting of lung transplantation.

本研究旨在确定在收获期间将NF-kB诱骗转染到同种异体移植物中是否会减少一氧化氮（NO）的产生并改善急性肺排斥反应。采用褐挪威大鼠（RT1n）和Lewis大鼠（RT1I）对进行左肺移植。所有同种异体移植物用含有日本血凝病毒（HVJ）脂质体- NF-kB诱饵（n=6）的odns复合物的PBS溶液（20 ml）冲洗，4℃保存60分钟，以混乱诱饵（n=5）和简单PBS溶液（n=5）作为对照。在不使用免疫抑制剂的情况下，移植5 d后，测定移植物呼出NO、气体交换和组织学排斥评分。与对照组相比，NF-kB诱导转染组呼出NO水平显著降低（445±162比1305±123 ppb， p<0.02）， PaO2（197±28比60±18 mmHg， p<0.02）和排斥反应评分（1.6±0.4比2.5±0.4）改善。ODNs诱骗转染供体肺抑制同种异体移植物NF-kB活化可改善急性同种异体移植物排斥反应中的肺损伤。这一结果暗示了一个可能的治疗靶点的alloo -independent途径，这似乎是可行的结合免疫抑制在肺移植的临床设置。