The Role of Tissue Factor (TF) In the development of Ischemic-reperfusion injury in Organ Transplantation

组织因子（TF）在器官移植缺血再灌注损伤发展中的作用

• 批准号: 12671168
• 负责人: YOSHIMURA Norio
• 金额: $ 1.98万
• 依托单位: Kyoto Prefectural University of Medicine
• 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 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671168/
• 关键词: Tissue Factor; ischemic-reperfusion injury; Organ Transplantation; アンチセンス法; TISSUE FACTOR; 腎; 組織因子(TF); TFPI; アンチセンス

(Background.) Tissue factor (TF) is an initiation factor for blood coagulation, and its expression is induced on endothelial cells during inflammatory or immune responses. We designed an antisense oligodeoxynucleotide (AS-1/TF) for rat TF, and studied its effect on hepatic ischemic reperfusion injury(Methods.) AS-1/TF was delivered intravenously to Lewis rats. After 10 hours, hepatic artery and portal vein were partially clamped. Livers were reperfused after 180 minutes and were harvested. TF expression was studied using immunohistochemical staining(Result.) One of 10 rats survived in a 5-day survival rates and TF was strongly stained on endothelial cells in nontrearment group. However, by treatment with AS-1/TF, six of seven survived and TF staining was significantly reduced. Furthermore, we observed that fluoroscein labeled AS-1/TF was absorbed into endothelial cells.(Conclusions.) These results suggest that AS-1/TF can strongly suppress the expression of TF and thereby inhibit ischemic reperfusion injury to the rat liver

（背景）组织因子（TF）是凝血的起始因子，其表达是在炎症或免疫反应期间在内皮细胞上诱导的。我们为大鼠TF设计了反义寡聚脱氧核苷酸(AS-1/TF)，并研究了其对肝脏缺血再灌注损伤的影响(方法)。将AS-1/TF静脉注射给Lewis大鼠。 10小时后，部分夹闭肝动脉和门静脉。 180分钟后重新灌注肝脏并收获。使用免疫组织化学染色研究TF表达(结果)。5天存活率中10只大鼠中有1只存活，并且未治疗组的内皮细胞上TF强烈染色。然而，通过 AS-1/TF 处理，七分之六存活下来，并且 TF 染色显着减少。此外，我们还观察到荧光素标记的AS-1/TF被内皮细胞吸收。（结论）这些结果表明AS-1/TF可以强烈抑制TF的表达，从而抑制大鼠肝脏的缺血再灌注损伤。

项目成果

MASAHIKO OKAMOTO: "USE OF ALLOCHIMERIC PROTEINS TO MITIGATE GRAFT-VERSUS-HOST AND HOST-VERSUS-GRAFT IMMUNE RESPONSES TO RAT SMALL BOWEL ALLOGRAFTS"TRANSPLANTATION. 7・70. 1060-1067 (2000)

MASAHIKO OKAMOTO：“使用同种嵌合蛋白减轻大鼠小肠同种异体移植物的移植物抗宿主和宿主抗移植物免疫反应”7・70。

Ushigome H, Sano H, Okamoto M, Kadotani Y, Nakamura K, Akioka K, Yoshimura R, Ohmori Y, Yoshimura N.: "The Role of Tissue Factor in Renal Ischemic Reperfusion Injury of the Rat"JOURNAL OF SURGICAL RESEARCH. 102. 102-109 (2002)

Ushigome H、Sano H、Okamoto M、Kadotani Y、Nakamura K、Akioka K、Yoshimura R、Ohmori Y、Yoshimura N.：“组织因子在大鼠肾缺血再灌注损伤中的作用”外科研究杂志。

Nakamura K, Kadotani Y, Ushigome H, Akioka K, Okamoto M, Ohmori Y, Yaoi T, Fushiki S, Yoshimura R, Yoshimura N.: "Antisense Oligonucleotide for tissue factor inhibits hepatic ischemic reperfusion injury"Biochemical and Biophysical Research Communications.

Nakamura K、Kadotani Y、Ushigome H、Akioka K、Okamoto M、Ohmori Y、Yaoi T、Fushiki S、Yoshimura R、Yoshimura N.：“组织因子反义寡核苷酸抑制肝缺血再灌注损伤”生物化学和生物物理研究通讯。

Matsuyama M, Akioka K, Okamoto M, Kadotani Y, Nakamura K, Ushigome H, Ohmori Y, Yoshimura R, Nakatani T, Yoshimura N: "CONTROL OF RENAL ISCHEMIC REPERFUSION INJURY BY ANTISENSE OLIGODEOXYNUCLEOTIDE OF TISSUE FACTOR"Transplantation Proceeding. (In press).

Matsuyama M、Akioka K、Okamoto M、Kadotani Y、Nakamura K、Ushigome H、Ohmori Y、Yoshimura R、Nakatani T、Yoshimura N：“组织因子反义寡脱氧核苷酸控制肾缺血再灌注损伤”移植论文集。

吉村了勇: "臓器移植とチトクロームP450(CYD)-特に免疫抑制薬のCYPを介した薬物相互作用について-"日本移植学会雑誌「移植」. 35号. 49-56 (2000)

Ryoyu Yoshimura：“器官移植和细胞色素P450（CYD）-特别是CYP介导的免疫抑制药物的药物相互作用-”日本移植学会杂志“移植”第35. 49-56号（2000）。