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.

因此，寻找一种有效的治疗方法来降低ALF的发病率和死亡率，为肝移植或肝再生提供一个有效的途径。HMGB 1最近被确定为各种急、慢性炎症的重要介质，而sRAGE是HMGB 1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已知作为HMGB 1竞争性抑制剂的HMGB 1 Box-A蛋白氨基酸的腺病毒载体。然后，经门静脉途径将该载体注射到急性肝衰竭大鼠模型中，结果显示，转染后的大鼠肝酶、血浆HMGB 1水平降低，肝组织学改变和存活率明显改善。

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