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

很明显，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。我们关注高迁移率组box1（HMGB1）和sRAGE。HMGB1最近被发现是多种急慢性炎症的重要介质，而sRAGE是HMGB1的可溶性受体。虽然制备编码sRAGE氨基酸的腺病毒载体比较困难，但我们成功地制备了编码HMGB1 Box-A蛋白氨基酸的腺病毒载体，该蛋白是HMGB1的竞争性抑制剂。将该载体经门静脉注射于急性肝衰竭大鼠体内。转染后的大鼠肝酶、血浆HMGB1明显降低，组织学表现和生存率明显提高。

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.