Developmental Research on Preservation of Liver Graft by Improving the Hepatic Microcirculation

本课题研究了肝微循环在肝移植再灌注损伤中的作用和肝移植供肝的保存条件，并利用肝窦内的Ito细胞和Kupffer细胞研究了肝微循环对肝窦血流的调控机制。免疫组织化学染色显示，Ito细胞内分布丰富的肌动蛋白、肌球蛋白和结蛋白等收缩蛋白。血管活性物质内皮素-1的加入引起Ito细胞的收缩，并且这种收缩活性被认为有助于窦状收缩和血流控制。枯否细胞对肌动球蛋白系统具有吞噬活性，枯否细胞摄入异物后可阻断窦状隙血流。结果表明，肝表面氧合状况是预测肝移植术后再灌注损伤的最佳指标，而UW液是肝移植术后的标准保存液，为了更好地保存肝脏，我们研制了一种新的“卡罗莱纳冲洗液”。美国马约诊所已开始临床试验，以评估该溶液对肝移植的益处。

In this project, we investigated (1)the role of hepatic microcirculation on the re-perfusion injury and (2)the preservation condition for the graft in liver transplantation.The mechanisms to control sinusoidal blood flow were investigated using cultured Ito cells and Kupffer cells which exist in sinusoid. Immunohistochemical staining revealed that contractile proteins such as actin, myosin and desmin were richly distributed in Ito cells. Addition of vasoactive substance, endothelin-1, caused the contraction of Ito cells and this contractile activity was thought to contribute on sinusoidal contraction and control of blood flow. Kupffer cells showed active phagocytic activity with the actomyosin system and Kupffer cells with ingested foreign substances might block the sinusoidal blood flow. The predictive factors for the re-perfusion injury was investigated and revealed that the oxygenation of the surface of the liver was a best available for prediction of the prognosis of liver transplantation.Although, the UW solution is standard for the liver preservation, we developed a new solution called "Carolina Rinse solution" for the better preservation. The clinical trial to assess the benefit of this solution for the liver transplantation has begun in Mayo Clinic in USA.