Yokoyama Yukihiro, Nimura Yuji, Nagino Masato, Bland Kirby I, Chaudry Irshad H
Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Arch Surg. 2005 Aug;140(8):801-7. doi: 10.1001/archsurg.140.8.801.
Hepatic injury after hepatic stress is caused by several mechanisms, including inflammatory reaction and microcirculatory disturbance. Levels of thromboxane, a vasoconstrictive eicosanoid, have been shown to increase in systemic circulation after different types of hepatic stress such as endotoxemia, hepatic ischemia-reperfusion, hepatectomy, liver transplantation, hemorrhagic shock and resuscitation, hepatic cirrhosis, and alcoholic liver injury. The production of thromboxane from the liver is also enhanced under these stresses, which may act on the liver in an autocrine or a paracrine fashion. Kupffer cells, resident hepatic macrophages, may be a major source of stress-induced thromboxane, although other cell types in the liver such as sinusoidal endothelial cells and hepatocytes may also produce this eicosanoid. Thromboxane induces hepatic damage through vasoconstriction, platelet aggregation, induction of leukocyte adhesion, up-regulation of proinflammatory cytokines, and induction of other vasoconstrictor release. In this regard, administration of cyclooxygenase inhibitor, specific thromboxane synthase inhibitor, and specific thromboxane receptor antagonists has been shown to protect from severe hepatic injury elicited by these hepatic stresses. Furthermore, blockade of Kupffer cell function by administration of gadolinium chloride showed salutary effects in preventing hepatic damage in bile duct ligation models. This review article summarizes the recent knowledge of the role of thromboxane in various types of hepatic stress and the effects of thromboxane inhibitors in these models.
肝脏应激后的肝损伤由多种机制引起，包括炎症反应和微循环障碍。血栓素是一种血管收缩性类花生酸，在内毒素血症、肝脏缺血再灌注、肝切除术、肝移植、失血性休克与复苏、肝硬化及酒精性肝损伤等不同类型的肝脏应激后，其在体循环中的水平已被证实会升高。在这些应激状态下，肝脏中血栓素的生成也会增强，它可能以自分泌或旁分泌的方式作用于肝脏。库普弗细胞，即肝脏中的常驻巨噬细胞，可能是应激诱导的血栓素的主要来源，不过肝脏中的其他细胞类型，如窦状内皮细胞和肝细胞，也可能产生这种类花生酸。血栓素通过血管收缩、血小板聚集、诱导白细胞黏附、上调促炎细胞因子以及诱导其他血管收缩剂释放来诱导肝损伤。在这方面，已证实给予环氧化酶抑制剂、特异性血栓素合酶抑制剂和特异性血栓素受体拮抗剂可保护机体免受这些肝脏应激引发的严重肝损伤。此外，在胆管结扎模型中，给予氯化钆阻断库普弗细胞功能对预防肝损伤有有益作用。这篇综述文章总结了血栓素在各种类型肝脏应激中的作用以及血栓素抑制剂在这些模型中的作用的最新知识。
