Institute of Basic Medical Sciences, National Chang Kung University, Tainan, Taiwan.
J Transl Med. 2010 Dec 21;8:138. doi: 10.1186/1479-5876-8-138.
Biliary atresia (BA) is a typical cholestatic neonatal disease, characterized by obliteration of intra- and/or extra-hepatic bile ducts. However, the mechanisms contributing to the pathogenesis of BA remain uncertain. Because of decreased bile flow, infectious complications and damaging endotoxemia occur frequently in patients with BA. The aim of this study was to investigate endotoxin levels in patients with BA and the relation of these levels with the expression of the endotoxin receptor, CD14.
The plasma levels of endotoxin and soluble CD14 were measured with a pyrochrome Limulus amebocyte lysate assay and enzyme-linked immunosorbent assay in patients with early-stage BA when they received the Kasai procedure (KP), in patients who were jaundice-free post-KP and followed-up at the outpatient department, in patients with late-stage BA when they received liver transplantation, and in patients with choledochal cysts. The correlation of CD14 expression with endotoxin levels in rats following common bile duct ligation was investigated.
The results demonstrated a significantly higher hepatic CD14 mRNA and soluble CD14 plasma levels in patients with early-stage BA relative to those with late-stage BA. However, plasma endotoxin levels were significantly higher in both the early and late stages of BA relative to controls. In rat model, the results demonstrated that both endotoxin and CD14 levels were significantly increased in liver tissues of rats following bile duct ligation.
The significant increase in plasma endotoxin and soluble CD14 levels during BA implies a possible involvement of endotoxin stimulated CD14 production by hepatocytes in the early stage of BA for removal of endotoxin; whereas, endotoxin signaling likely induced liver injury and impaired soluble CD14 synthesis in the late stages of BA.
胆道闭锁（BA）是一种典型的新生儿胆汁淤积性疾病，其特征为肝内和/或肝外胆管阻塞。然而，导致 BA 发病机制的机制仍不清楚。由于胆汁流量减少，BA 患者常发生感染性并发症和破坏性内毒素血症。本研究旨在探讨 BA 患者的内毒素水平及其与内毒素受体 CD14 表达的关系。
采用焦虫 Limulus amebocyte lysate assay 和酶联免疫吸附试验检测早期 BA 患者行 Kasai 手术（KP）时、KP 后黄疸消退并在门诊随访的患者、晚期 BA 患者行肝移植时以及胆总管囊肿患者的血浆内毒素和可溶性 CD14 水平。研究了胆总管结扎后大鼠 CD14 表达与内毒素水平的相关性。
结果表明，早期 BA 患者的肝 CD14 mRNA 和可溶性 CD14 血浆水平明显高于晚期 BA 患者。然而，早期和晚期 BA 患者的血浆内毒素水平均明显高于对照组。在大鼠模型中，结果表明胆总管结扎后大鼠肝组织内毒素和 CD14 水平均明显升高。
BA 期间血浆内毒素和可溶性 CD14 水平的显著增加表明，内毒素可能刺激肝细胞产生 CD14，以清除内毒素，这可能与 BA 的早期阶段有关；而在 BA 的晚期阶段，内毒素信号可能诱导肝损伤和可溶性 CD14 合成受损。
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