肝硬化患者小肠细菌过度生长与外周血内毒素水平、TLR2、TLR4表达的关系

Relationship between Small Intestinal Bacterial Overgrowth and Endotoxemia Levels and TLR2, TLR4 Expression in Patients with Cirrhosis

目的 探讨肝硬化患者小肠细菌过度生长与内毒素及TLR2、TLR4表达的关系。方法 58例肝硬化患者和26例健康志愿者,采用显色基质鲎试剂试管法检测外周血内毒素浓度,流式细胞术检测外周血PBMC表面TLR2、TLR4的表达,乳果糖氢呼气试验(LHBT)评估小肠细菌过生长情况。结果 肝硬化组SIBO发生率为43.10%,显著高于健康对照组的7.69%(χ~2=10.32,P=0.001);肝硬化组LHBT小肠集值、外周血内毒素浓度、TLR2、TLR4高于健康对照组(t值分别为11.573、9.958、12.380、10.319,P均<0.05);在肝硬化患者中SIB0阳性患者LHBT集值、外周血内毒素浓度、TLR2、TLR4水平高于SIBO阴性患者(t值分别为12.746、8.067、11.804、6.258,P均<0.05)。Pearson相关分析结果显示,肝硬化组、肝硬化SIBO阳性组的LHBT小肠集值与内毒素浓度、TLR2、TLR4呈正相关(P均<0.05),且内毒素浓度与TLR2和TLR4呈正相关(P均<0.05)。结论 肝硬化患者小肠细菌过度生长更易出现高内毒素血症,并通过TLR2、TLR4的高表达引发炎症损伤,加重肝硬化病情。

Objective To determine the frequency of SIBO in cirrhotics and correlate with endotoxemia,TLR2,TLR4 expression.Methods Totally 58 patients with cirrhosis were selected as observation group,and 26 healthy volunteers were selected as control group.The serum endotox were tested by TAL chromogenic substrate Assay（the chromogenic substrate Limulus amebocyte lysate test）. The expression of TLR2,TLR4 on the surface of PBMC were tested by flow cytometry. Small-intestinal bacterial overgrowth was determined by lactulose hydrogen breath test（LHBT）. Results Of the 58 cirrhotics,25（43. 0%） had SIBO positive,compared to two（7.69%）control（χ^2= 10.32,P = 0.001）. The LHBT intestinal set value,serum endotox level and the expression TLR2,TLR4 on the surface of PBMC in cirrhosis were obviously higher than the control group（t = 11.573,P〈0.05; t = 9.958,P〈0.05; t = 12.380,P〈0.05; t =10.319,P〈0.05）. It was shown by Pearson correlation analysis that LHBT intestinal set value was positive correlated with endotox level and the expression TLR2,TLR4 among cirrhotic patients and live cirrhosis with SIBO-negative. Conclusion SIBO is associated with endotoxemia,and through TLR2,TLR4 signaling pathways lead to inflammatory damage,its frequency increased with increase in severity of cirrhosis.