Hoshino Sumito, Sun Zhaoli, Uchikura Keiichiro, Tsugane Kyoji, Ceppa Eugene, Bulkley Gregory B, Klein Andrew S
Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
J Gastrointest Surg. 2003 May-Jun;7(4):497-506. doi: 10.1016/S1091-255X(03)00025-8.
Septic complications are common in patients with biliary obstruction. This is thought to be related, in part, to dysfunction of the hepatic reticuloendothelial system (RES). It has been reported that nearly 80% of circulating microorganisms are phagocytosed and killed within the liver and that clearance of circulating pathogens is significantly impaired in patients with jaundice. However, the effect of biliary obstruction specifically on phagocytic killing within the liver is less well described. Therefore this study was designed to quantify the effect of biliary obstruction, simultaneously and discriminately, on two important components of hepatic RES function (phagocytosis and phagocytic killing). Rats were divided into three experimental groups: control, sham, and jaundiced (common bile duct ligation). At 7, 10, 14, and 21 days after operation, E. coli labeled with both 125I and 51Cr were injected intravenously. Using the previously validated double-labeled in vivo E. coli technique, hepatic phagocytic clearance (HPC), hepatic killing efficiency (HKE), and net hepatic killing (NHK) were measured. Common bile duct ligation resulted in a significant decrease in the HPC of E. coli 10, 14, and 21 days postoperatively. Similarly, HKE was significantly decreased in jaundiced animals by postoperative day 10, but returned to baseline values by day 14. The net effect of these changes in HPC and HKE values were reflected in a significant reduction in NHK in jaundiced animals. Results of the present study suggest that obstructive jaundice impairs both phagocytosis and phagocytic killing within the liver. These findings may help to explain the susceptibility of patients with biliary tract obstruction to the morbidity and mortality of septic complications.
脓毒症并发症在胆道梗阻患者中很常见。这被认为部分与肝网状内皮系统(RES)功能障碍有关。据报道,近80%的循环微生物在肝脏内被吞噬和杀灭,而黄疸患者循环病原体的清除明显受损。然而,胆道梗阻对肝脏内吞噬杀伤的具体影响描述较少。因此,本研究旨在同时且分别量化胆道梗阻对肝RES功能的两个重要组成部分(吞噬作用和吞噬杀伤)的影响。将大鼠分为三个实验组:对照组、假手术组和黄疸组(胆总管结扎)。在术后7、10、14和21天,静脉注射用125I和51Cr标记的大肠杆菌。使用先前验证的双标记体内大肠杆菌技术,测量肝脏吞噬清除率(HPC)、肝脏杀伤效率(HKE)和肝脏净杀伤率(NHK)。胆总管结扎导致术后10、14和21天大肠杆菌的HPC显著降低。同样,黄疸动物术后第10天HKE显著降低,但到第14天恢复到基线值。HPC和HKE值的这些变化的净效应反映在黄疸动物NHK的显著降低上。本研究结果表明,梗阻性黄疸会损害肝脏内的吞噬作用和吞噬杀伤。这些发现可能有助于解释胆道梗阻患者易发生脓毒症并发症的发病和死亡情况。