Basic and clinical study for posthepatectomy liverfailure associated with bacterial infection

近年来广泛的肝切除术已被用于治疗肝胆恶性肿瘤。然而，细菌感染有时会导致术后肝功能衰竭，这是手术死亡的主要原因。本研究探讨了细菌感染引起的各种细胞因子和热休克蛋白（Hsp）引起肝细胞损伤的机制。由脂多糖诱导的枯否细胞（巨噬细胞）产生肿瘤坏死因子（TNF）-α和白细胞介素（IL）-12，它们是肝细胞损伤的主要触发因素。二丁酰环磷酸腺苷（cAMP）和前列腺素E2诱导细胞内cAMP，抑制肝细胞损伤。我们提出了一种解释，增加细胞内cAMP诱导IL-β和热休克蛋白70抑制TNF-α和TL-12。然而，这些细胞因子（TNF-α、IL-12和干扰素γ）也激活巨噬细胞以排除细菌。因此，诱导细胞内cAMP的治疗也可能间接抑制细菌抗性。为预防细菌感染引起的肝衰竭，应采取保护肝细胞的方法，保留其抗细菌机制。

Recently extensive liver resection has been performed for treatment of hepatobiliary malignancies. However, bacterial infection sometimes results in posthepatectomy liver failure which is a major cause of operative death. We have investigated mechanisms of hepatocyte injury caused by various cytokines and heat shock protein (Hsp) which derived from bacterial infection. Kupffer cells (macrophages) induced by lipopolysaccharide produce tumor necrosis factor (TNF)-alfa and interleukin (IL)-12 which are main triggers for hepatocyte injury. Dibutyryl cyclic adenosine monophosphate (cAMP) andprostaglandin E2 induce intracellular cAMP and inhibit hepatocyte injury. We propose an explanation that increased intracellular cAMP induces IL-b and Hsp 70 which inhibit TNF-alfa and TL-12. However, these cytokines (TNF-alfa, IL-12 and interferon gamma) also activate macrophages to exclude bacteria. So, treatments which induce intracellular cAMP may also indirectly inhibit bacterial-resistant properties. In order to prevent hepatic failure caused by bacterial infection, we should make a method of hepatocyte protection which preserve bacteria-fighting mechanisms.