Suppression of hepatic ischemia/reperfusion injury using RNA

利用 RNA 抑制肝缺血/再灌注损伤

• 批准号: 13671304
• 负责人: UMESHITA Koji
• 金额: $ 2.24万
• 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: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671304/
• 关键词: liver; ischemia; reperfusion; gene therapy; RNA; HVJ eavelope vector; HVJ-liposome; bcl-2; 肝虚血・再潅流傷害; mRNA; bcl-2; DNA; 遺伝子導入; 肝細胞内導入; HVJ-リポゾーム

Effective method for transferring bcl-2 mRNA into rat liver in vivo was investigated. We had developed a simple method for converting the lipid envelope of an inactivated virus to gene transfer vector. Hemagglutinating virus of Japan (HVJ) envelope vector was constructed by incorporating mRNA into inactivated HVJ particles. We injected HVJ envelope vector containing luciferase mRNA or lacZ mRNA to the liver via portal vein in Wistar rats and observed expression of protein in the liver 24 hours later. Further experiments have been performed to know the relationship between the amount of mRNA and onset, amount, and duration of protein expression in the liver, and we could decide the best method for our primary purpose. In the next step of our study, we are going to introduce bcl-2 mRNA into the rat liver using the above-mentioned method and investigate its effect on ischemia/reperfusion injury of the liver. This method may be further applied to cold storage/transplantation model of the rat.

目的：探讨bcl2mRNA体内导入大鼠肝脏的有效方法。我们开发了一种简单的方法，将灭活病毒的脂膜转化为基因转移载体。通过在灭活的日本血凝病毒(HVJ)颗粒中掺入信使核糖核酸(MRNA)，构建了日本血凝病毒包膜载体。将含有荧光素酶或LacZ基因的包膜载体经门静脉注入Wistar大鼠肝脏，24小时后观察其在肝脏中的表达。进一步的实验已经了解了mRNA的数量与肝脏蛋白质表达的开始、数量和持续时间的关系，我们可以决定最好的方法来达到我们的主要目的。在下一步的研究中，我们将用上述方法将bcl2mRNA导入大鼠肝脏，并观察其对肝脏缺血再灌注损伤的影响。该方法可进一步应用于大鼠的冷藏/移植模型。

项目成果

Kaneda, Y.: "HVJ (hemagglutinating virus of Japan) envelope vector as a versatile gene delivery system"Mol Ther. 6・2. 219-226 (2002)

Kaneda，Y.：“HVJ（日本血凝病毒）包膜载体作为多功能基因传递系统”Mol Ther 6·2（2002）。

Suzuki, K.: "Human cytomegalovirus immediate-early protein IE2-86, but not IE1-72, causes graft coronary arteriopathy in the transplanted rat heart"Circulation. 106・12. 158-162 (2002)

Suzuki, K.：“人类巨细胞病毒立即早期蛋白 IE2-86，而非 IE1-72，导致移植大鼠心脏移植冠状动脉病”，循环 106・12。

Kaneda, Y. et al.: "HVJ (hemagglutinating virus of Japan) envelope vector as a versatile gene delivery system"Mol Ther. 6(2). 219-226 (2002)

Kaneda, Y. 等人：“HVJ（日本血凝病毒）包膜载体作为多功能基因传递系统”Mol Ther。