Antisense Therapy for Reperfusion Injury following Liver Transplantation

反义疗法治疗肝移植术后再灌注损伤

• 批准号: 06671188
• 负责人: IWAI Takehisa
• 金额: $ 1.41万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671188/
• 关键词: Antisense Therapy; Liver Transplantation; Reperfusion Injury; 再潅流障害; アンチセンス; リポゾーム

To select appropriate antisense probe, the following oligonucleotides were examined ; 17mer-1-PO,PS,PS3 and 17mer-2-PO,18mer-PS3,30mer-PS3 for TNFalpha, P50-PS3, P65-PS3 and triplex forming oligonucleotides for NF-kB.Antisense effect on TNFalpha Production was examined using RAW264 cell-lines with LPS stimulation. None of these antisenses showed effective suppression.Oligonucleotide uptake by liposomes was not so enough. We failed to get effective antisense liposome for in vivo study. In this study, we succeeded to detect signals from TNFalpha mRNA by in situ hybridization.This method will be used in clinic in the near future.

为了选择合适的反义探针，检测了以下寡核苷酸：TNF α的17 mer-1-PO、PS、PS3和17 mer-2-PO、18 mer-PS3、30 mer-PS3，P50-PS3、P65-PS3和NF-κ B的三链形成寡核苷酸。这些反义核酸均未表现出有效的抑制作用，脂质体对寡核苷酸的摄取也不充分。目前尚未能制备出有效的反义脂质体用于体内研究。本研究成功地应用原位杂交技术检测了肿瘤坏死因子α mRNA的信号，该方法有望应用于临床。