Anti-inflammatory cytokine gene transfection into allo graft organ

抗炎细胞因子基因转染同种异体移植器官

• 批准号: 09470257
• 负责人: KITAJIMA Masaki
• 金额: $ 7.74万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470257/
• 关键词: IL-1Ra; Ischemia-reperfusion injury; Liver transplantation; Gene therapy; Adenoviral vector; Lipofection; in vivo gene delivery; cytokine; IL-1Rg; 肝移植; サイトカイン; アデノウイルスベクター; 部分肝移植

We have recently reported that an anti-inflammatory cytokine, interleukin-1 receptor antagonist (IL-1Ra) reduces hepatic ischemia-reperfusion injury. The aim of this study is to investigate the effect of the IL-1Ra gene delivery into the rat liver on hepatic ischermia-reperfusion injury. The IL-1Ra cDNAs were delivered into the rat liver in vivo by the aid of plasmid/cationic liposome (lipofection) or recombinant adenoviral vector. Expression of the delivered gene was evaluated by histochemistry or by measuring the concentration of human IL-1Ra protein in rat serum by ELISA.The protective effect of IL-1Ra gene delivery on the hepatic ischemia-reperfusion injury was then evaluated by comparing serum ALT/AST and rat IL-6 or TNF levels and subsequent 7 days survival rate between IL-1Ra gene- and LacZ reporter gene-delivered groups. Our results demonstrated that 24 hours after gene delivery, serum IL-1Ra protein concentration was significantly elevated. Furthermore, 3 hours after hepatic ischemia-reperfusion, serum ALT/AST and rat TNF levels were significantly reduced and the survival rate was significantly higher in the IL-1Ra delivered group as compared with control group. Successful IL-1Ra gene delivery into the liver may be applicable to reduce the rejection after liver transplantation as well as hepatic isehemia-reperfusion injury.

我们最近报道了一种抗炎细胞因子，白细胞介素-1受体拮抗剂（IL-1Ra）可减少肝缺血-再灌注损伤。本研究旨在探讨IL-1Ra基因注入大鼠肝脏后对肝缺血再灌注损伤的影响。IL-1Ra cdna通过质粒/阳离子脂质体（脂质体感染）或重组腺病毒载体在体内传递到大鼠肝脏。通过组织化学或ELISA法测定大鼠血清中人IL-1Ra蛋白的浓度来评价传递基因的表达。通过比较IL-1Ra基因传递组和LacZ报告基因传递组血清ALT/AST和大鼠IL-6或TNF水平及随后7天存活率，评估IL-1Ra基因传递对肝缺血再灌注损伤的保护作用。我们的研究结果表明，基因传递后24小时，血清IL-1Ra蛋白浓度显著升高。肝缺血再灌注3 h后，IL-1Ra给药组血清ALT/AST和大鼠TNF水平明显低于对照组，生存率明显高于对照组。IL-1Ra基因成功进入肝脏可用于减少肝移植后的排斥反应以及肝脏缺血再灌注损伤。

项目成果

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