Development of a new effective therapy of ischemia reperfusion injury of liver and small intestine.

开发一种新的有效治疗肝脏和小肠缺血再灌注损伤的方法。

• 批准号: 23591875
• 负责人: SINODA Masahiro
• 金额: $ 3.33万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591875/
• 关键词: HMGB1; sRAGE; 肝虚血再灌流; 肝移植; 肝細胞移植; 肝虚血再灌流障害モデル; 移植・再生医療; ウィルス; 遺伝子; バイオリアクター

It is clear that the development of an effective therapy, which would serve as a bridge to liver transplantation or regeneration, is needed to reduce the morbidity and mortality associated with ALF.We paid attention to High-mobility group box1(HMGB1) and sRAGE. HMGB1 has recently been identified as an important mediator of various kinds of acute and chronic inflammation and sRAGE is the soluble receptor of HMGB1.Although it was difficult to make adenovirus vector which encoded amino acids of sRAGE, we suceeded in making adenovirus vector which encoded amino acids of HMGB1 Box-A protein known to act as a competitive inhibitor of HMGB1.Then,the vector was injcected via the portal vein in rats with acute liver failure.Transfected rats showed decreased hepatic enzymes, plasma HMGB1, and histological findings and survival were significantly improved.

显然，需要开发一种有效的治疗方法，作为肝移植或再生的桥梁，以降低与 ALF 相关的发病率和死亡率。我们关注高迁移率族蛋白盒 1 (HMGB1) 和 sRAGE。 HMGB1最近被认为是多种急、慢性炎症的重要介质，而sRAGE是HMGB1的可溶性受体。虽然很难制备编码sRAGE氨基酸的腺病毒载体，但我们成功制备了编码氨基酸的腺病毒载体。已知可作为 HMGB1 竞争性抑制剂的 HMGB1 Box-A 蛋白的酸。然后，通过门静脉将载体注射到急性肝病大鼠体内转染的大鼠表现出肝酶、血浆HMGB1下降，组织学检查结果和生存率显着改善。

项目成果

Effect of an omega-3 lipid emulsion in reducing oxidative stress in a rat model of intestinal ischemia-reperfusion injury.

• DOI: 10.1007/s00383-012-3144-0
• 发表时间: 2012-09
• 期刊: Pediatric surgery international
• 影响因子: 1.8
• 作者: Arisue A;Shimojima N;Tomiya M;Shimizu T;Harada D;Nakayama M;Tomita H;Shinoda M;Tanabe M;Maruyama I;Mizuno M;Kuroda T;Wakabayashi G;Morikawa Y
• 通讯作者: Morikawa Y

Pharmacokinetics of mizoribine in adult living donor liver transplantation

咪唑立宾在成人活体肝移植中的药代动力学

• 发表时间: 2012
• 期刊: Transplant Proc.
• 作者: Shinoda M;Tanabe M;Kawachi S;Ono Y;Hayakawa T;Iketani O;Kojima M; Fuchimoto Y
• 通讯作者: Fuchimoto Y