Miyagi S, Okada A, Oikawa K, Sato A, Fujimori K, Satomi S
Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Transplant Proc. 2008 Sep;40(7):2152-5. doi: 10.1016/j.transproceed.2008.06.010.
We sought to preserve the microcirculation as a keystone in liver transplantation from a non-heart-beating donor (NHBD). The purpose of this study was to investigate the cytoprotective effects of a serine protease inhibitor, nafamostat mesilate, and prostaglandin I2 (PGI2) on livers transplanted from NHBDs.
Male Wistar rats were used in five groups of nine rats each. In group 1, livers were retrieved from heart-beating donors (HB group); in group 2, livers were retrieved from NHBDs that had experienced agonal apnea (NHB group); in group 3, livers were retrieved in the same manner as in the NHBD group but were pretreated with nafamostat mesilate (NM), 0.2 mg/kg/h, (NM group); in group 4, livers were retrieved in the same manner as in the NHBD group but were pretreated with prostaglandin (PG) I2, 33 ng/kg/h for 30 minutes (PG group); and in group 5, livers were retrieved in the same manner as in the NHBD group but were pretreated with NM plus PG, (NM+PG group). Livers were perfused for 60 minutes with Krebs-Henseleit bicarbonate buffer after 6 hours of cold preservation, after which the perfusate and liver tissue were analyzed in one set of experiments. In another set of experiments, livers retrieved and after 1 hour of cold preservation were transplanted according to the Kamada method.
In the NM+PG group, the values of interleukin-1beta, tumor necrosis factor-alpha, and thromboxane B2 were significantly lower than those in the NHB group. At histologic analysis, sinusoidal endothelial cells were well preserved in the NM+PG group. The number of survivors at 7 days after liver transplantation in the 5 groups were 9, 0, 1, 1, and 3, respectively.
The serine protease inhibitor, NM, and PGI2 supported sinusoidal endothelial cells and preserved microcirculation.
我们试图将微循环作为非心脏跳动供体（NHBD）肝脏移植的关键要素加以保护。本研究的目的是调查丝氨酸蛋白酶抑制剂甲磺酸萘莫司他和前列腺素I2（PGI2）对NHBD肝脏移植的细胞保护作用。
雄性Wistar大鼠分为五组，每组九只。第1组，从心脏跳动供体获取肝脏（HB组）；第2组，从经历濒死呼吸暂停的NHBD获取肝脏（NHB组）；第3组，以与NHBD组相同的方式获取肝脏，但用甲磺酸萘莫司他（NM）0.2mg/kg/h进行预处理（NM组）；第4组，以与NHBD组相同的方式获取肝脏，但用前列腺素（PG）I2 33ng/kg/h预处理30分钟（PG组）；第5组，以与NHBD组相同的方式获取肝脏，但用NM加PG进行预处理（NM + PG组）。冷保存6小时后，肝脏用Krebs-Henseleit碳酸氢盐缓冲液灌注60分钟，之后在一组实验中对灌注液和肝组织进行分析。在另一组实验中，获取的肝脏冷保存1小时后，按照Kamada方法进行移植。
在NM + PG组中，白细胞介素-1β、肿瘤坏死因子-α和血栓素B2的值显著低于NHB组。组织学分析显示，NM + PG组的肝窦内皮细胞保存良好。五组肝脏移植后7天的存活大鼠数量分别为9只、0只、1只、1只和3只。
丝氨酸蛋白酶抑制剂NM和PGI2可支持肝窦内皮细胞并保护微循环。
