Marzi I, Cowper K, Takei Y, Lindert K, Lemasters J J, Thurman R G
Department of Pharmacology, University of North Carolina, Chapel Hill 27599-7365.
Transpl Int. 1991 Dec;4(4):215-20. doi: 10.1007/BF00649106.
The purpose of this study was to determine whether prevention of Kupffer cell activation following orthotopic liver transplantation improves postoperative survival. First, particle phagocytosis by Kupffer cells was monitored continuously from the uptake of colloidal carbon by the perfused liver. Unstored livers took up carbon at rates of around 150 mg/g per hour, whereas storage for 24 h in Euro-Collins solution nearly doubled values to about 290 mg/g per hour. Treatment of rats with methyl palmitate, an inhibitor of phagocytosis by Kupffer cells, reduced carbon uptake to about one-third to one-half of control values in unstored and stored livers, respectively. Oxygen uptake, which was increased about 25% in stored and unstored livers by infusion of colloidal carbon, was only increased 5%-10% in both groups following treatment with methyl palmitate, suggesting that Kupffer cell activation was prevented by methyl palmitate. In livers transplanted after storage for 6 h in Euro-Collins solution (nonsurvival conditions), control rats survived only about 12 h, while treatment with methyl palmitate increased survival time significantly--more than threefold--to about 40 h. These data are consistent with the hypothesis that activation of Kupffer cells following cold ischemic storage and reperfusion is an early event involved in liver graft failure.
本研究的目的是确定原位肝移植后预防库普弗细胞激活是否能提高术后生存率。首先，从灌注肝脏摄取胶体碳开始，持续监测库普弗细胞的颗粒吞噬作用。未储存的肝脏以每小时约150毫克/克的速率摄取碳，而在欧洲柯林斯溶液中储存24小时后，该值几乎翻倍，达到约290毫克/克每小时。用棕榈酸甲酯（一种库普弗细胞吞噬作用抑制剂）处理大鼠后，未储存和储存肝脏中的碳摄取量分别降至对照值的约三分之一至二分之一。通过输注胶体碳，储存和未储存肝脏中的氧摄取量增加了约25%，而在棕榈酸甲酯处理后，两组的氧摄取量仅增加了5%-10%，这表明棕榈酸甲酯可预防库普弗细胞激活。在欧洲柯林斯溶液中储存6小时后移植的肝脏（非存活条件），对照大鼠仅存活约12小时，而棕榈酸甲酯处理显著延长了存活时间——超过三倍——至约40小时。这些数据与以下假设一致，即冷缺血储存和再灌注后库普弗细胞的激活是肝移植失败的早期事件。
