Changes of bile canalicular contraction and of specific receptors on hepatocyte membrane during cholestasis in peri-operation.

a .脓毒症和胆汁淤积——窦道和胆小管的基本发现——肝功能障碍是脓毒症的不利病理生理条件之一，它是由大循环和微循环紊乱的改变以及肝内细胞系统功能衰竭引起的。肝衰竭过程中肝脏的典型反应已被广泛报道。然而，人们对其机制知之甚少；例如，胆汁淤积的发育机制，这是导致肝功能衰竭的特征。胆汁淤积性肝病是肝损伤的一种形式，在肝外胆管阻塞或肝内代谢异常后可促进肝硬化^2。脓毒症发生时胆汁淤积的基本发病机制是由于后一种原因，它是基于肝细胞内和细胞外胆红素运输系统的紊乱，受到肝实质细胞和肝窦壁细胞反应的影响。众所周知，相对于一般毛细血管或肾上腺窦，肝脏窦的结构具有血流与器官功能细胞之间信息交换的特点。探讨严重感染下胆汁淤积的发病机制有助于对该病的认识和今后的治疗。胆管是胆道树中最小的组成部分，位于相邻肝细胞的顶端表面之间。它们被肌动蛋白和肌凝蛋白包围，并具有收缩活性，这在促进胆汁通过小管途径运输方面起着重要作用。用损害肌动蛋白聚合和解聚的药物治疗大鼠，可导致胆汁分泌衰竭和检测胆管收缩。b .肿瘤坏死因子- α诱导大鼠胆管胆汁液渗漏外科医生有时会遇到高胆红素血症，但在胃肠道和/或肝脏手术后胆管没有任何物理阻塞。大多数病例伴有细菌感染和内毒素血症。已知Kupffer细胞在内毒素刺激下分泌炎性细胞因子，如肿瘤坏死因子- α(TNF- α)和白细胞介素-6（IL-6）。我们推测TNF- α和IL-6可能参与了高胆红素血症。方法：监测从大鼠肝脏分离的肝细胞偶联的胆小管收缩情况，每10秒延时成像2小时。取大鼠胆总管插管，取胆液。注射TNF- α和/或IL-6后灌注镧和固定液，观察肝脏超微结构。结果：在培养基中加入TNF- α后，偶联细胞间隙出现快速流。TNF- α和IL-6治疗组大鼠胆管收缩次数减少，收缩速度明显快于对照组。与对照组相比，注射TNF- α和/或IL-6的大鼠胆汁分泌明显减少。TNF-α-处理大鼠血清总胆汁酸浓度升高，镧在胆管内短暂积聚。结论：TNF- α可能使紧密的胆管结结构松动，胆液可能从胆管渗漏。少

A.Sepsis and Cholestasis---Basic findings in the sinusoid and in bile canaliculus---Hepatic dysfunction, as one of unfavorable the pathophysiologic condition in sepsis, is induced by the alterations in both macro- and microcirculatory disturbance and by functional failure in intrahepatic cellular system. The stereotypical response of the liver in the process of hepatic failure has been well reported. However, little is known in its mechanisms ; for example the developmental mechanism of cholestasis, which is characteristics as a result in hepatic failure^1. Cholestatic liver disease is one form of liver injury that promotes cirrhosis, follows extrahepatic bile duct obstruction or intrahepatic metabolic abnormalities^2. The essential pathogenesis of cholestasis developing during sepsis is due to the latter reason and is based on the disturbance of intra- and extra- cellular transportation system of bilirubin in hepatocytes, influenced by responses of the hepatic parenchymal cells and th … More e sinusoidal lining cells. There are well known that the structure of sinusoid in liver is characteristic in information-exchange between blood stream and the organ functional cells, in relative to those of general capillary vessels or the sinusoid of the adrenal gland. To investigate the pathogenesis of cholestasis under severe infection might contribute to the essential understanding of this condition and to future therapy. Bile canaliculi, the smallest components of the biliary tree lie between the apical surfaces of adjacent hepatocytes. They are surrounded by actin and myosin and possess contractile activity, which has a major role in facilitating the transport of bile through the canalicular route. Treatment of rats with drugs that impair polymerization and depolymerization of actin results in bile secretary failure and detective bile canalicular contraction.B.Tumor Necrosis Factor- α Induces Bile Juice Leakage from Rat Bile CanaliculiSurgeons sometimes encounter hyperbilirubinemia without any physical obstruction of the bile duct after operations on the gastrointestinal tract and/or liver. In most cases the patients have accompanying bacterial infections and endotoxemia. It is known that Kupffer cells are stimulated by endotoxins to secrete inflammatory cytokines such as tumor necrosis factor- α(TNF- α) and interleukin-6(IL-6). We hypothesized that TNF- α and IL-6 might be involved in the hyperbilirubinemia. Methods : Bile canalicular contractions of hepatocytes couplets isolated from rat livers were monitored and time-lapse images were taken every 10 sec for 2 hr. The common bile ducts of rats were cannulated and bile juice was collected. The livers, perfused with lanthanum and fixation solution after the injection of TNF- α and/or IL-6, were ultrastructurally examined. Results : Rapid streams at the intercellular spaces of couplets were observed when TNF- α was added to the medium. The number of bile canalicular contractions decreased in the couplets treated with TNF- α and IL-6, and the contractive velocity of bile canaliculi was faster than that of bile canaliculi in controls. Bile secretion of rats injected with TNF- α and/or IL-6 was significantly reduced compared with that of the control. In TNF-α-treated rats the total bile acid concentration of the serum increased and lanthanum temporarily accumulated in bile canaliculi. Conclusions : These results suggest that TNF- α may loosen the tight junctional structure and that bile juice may leak from bile canaliculi. Less