肝硬化患者的内毒素和脂多糖结合蛋白水平及其与预后的关系

The Levels of Endotoxin and Lipopolysaccharide Binding Protein in Patients with Cirrhosis and their Relevance to the Prognosis

背景脂多糖结合蛋白(LBP)是介导脂多糖(LPS)活化单核/巨噬细胞的关键因子。尽管内毒素在慢性肝病和肝硬化中具有重要作用,但其结合蛋白在肝硬化中的意义尚不清楚。目的了解肝硬化患者的内毒素和LBP水平,并探讨其与预后的关系。方法分别以基质显色法鲎试验和酶联免疫吸附测定(ELISA)检测肝硬化患者的血浆内毒素和LBP水平;伴腹水患者同时测定腹水内毒素和LBP水平,并进行2个月的短期随访,记录存活情况。结果肝硬化患者的血浆内毒素和LBP水平均显著高于健康对照者(P<0.05),其中伴腹水患者的血浆内毒素水平显著高于无腹水患者(P<0.05)。Child鄄PughC级肝硬化伴腹水患者的腹水内毒素水平显著高于B级患者(P<0.05),而B级患者的血浆LBP水平显著高于C级患者(P<0.05)。短期随访显示肝硬化伴腹水死亡患者的腹水内毒素水平显著高于存活者(P<0.05)。结论肝硬化患者的血浆内毒素和LBP水平均升高,LBP水平升高可能是对肝硬化肠源性内毒素血症的一种持续的慢性炎症应答。腹水内毒素水平可以作为肝硬化伴腹水患者短期生存的一个预测指标。

Background: Lipopolysaccharide binding protein (LBP) is a key factor that mediates lipopolysaccharide (LPS) activation of monocytes and macrophages. Although the endotoxins play important roles in the chronic liver diseases and cirrhosis, the significance of the endotoxin binding protein in cirrhosis remains unclarified. Aims: To appraise the endotoxin and LBP levels in patients with cirrhosis, and to investigate their relevance to the prognosis. Methods: The plasma levels of endotoxin and LBP in cirrhotic patients were determined by chromogenic substrate Limulus amebocyte lysate assay and enzyme-linked immunosorbent assay (ELISA), respectively. Ascitic fluid levels of endotoxin and LBP were determined in cirrhotic patients with ascites. All cirrhotic patients with ascites were followed up for two months, and their survival data were recorded. Results: The plasma levels of endotoxin and LBP in cirrhotic patients were significantly higher than those in healthy controls (P<0.05). In addition, patients with ascites showed higher level of plasma endotoxin than those without ascites (P<0.05). Among the ascitic cirrhotic patients, those with Child-Pugh grade C showed higher level of ascitic fluid endotoxin and lower level of plasma LBP than those with Child-Pugh B (P<0.05); and in short-term survival analysis, the ascitic fluid endotoxin level was significantly higher in non-survivors than those in survivors (P<0.05). Conclusions: In cirrhotic patients both the plasma levels of endotoxin and LBP are increased, and the elevation of LBP level may be a continuous chronic inflammatory response to enterogenic endotoxemia. The ascitic fluid endotoxin level may be served as a predicting index for short-term survival in cirrhotic patients with ascites.