肝肺综合征患者外周血单核细胞Toll样受体2和一氧化氮合酶的表达及其意义

目的 探索内毒素(LPS)、Toll样受体2(TLR2)、诱导型一氧化氮合酶(iNOS)在肝肺综合征(HPS)发生发展机制中的作用.方法 将研究对象分为肝肺综合征组(HPS组,31例,其中26例行肝移植术)、非肝肺综合征组(即未合并HPS的终末期肝病组,30例,均行肝移植术)和正常对照组(10名健康志愿者).各组患者分别于术前、术后3、7、14、21、28 d检测外周血LPS、Toll样受体2mRNA(TLB2mRNA)及诱导型一氧化氮合酶mRNA(iNOSmRNA)表达水平,及其肝随移植术后肝功能及低氧血症好转的术后变化.结果 HPS组术前LPS,TLR2mRNA,iNOSmBNA的表达水平较非HPS组高,但差异无统计学意义(P0.05);而HPS组术前LPS,TLR2mRNA,iNOSmRNA的表达均较正常对照组明显升高(P<0.05);非HPS组LPS,TLR2mRNA,iNOSmRNA的表达均较正常对照组高,但差异无统计学意义(P0.05).HPS与非HPS组的终末期肝病患者行肝移植术后,随肝功能的改善,TLR2mRNA表达呈下降趋势,呼吸和血氧饱和度亦逐步改善.结论 终末期肝病肠源性内毒素释放及其导致的TLR2mRNA和iNOSmRNA表达的增高可能是肝肺综合征的重要发病机制.

Significance of lipopolysaccharides, toll-like receptor and inducible nitric oxide synthase in hepatopulmonary syndrome

Objective To investigate the role of lipopolysaccharides (LPS), toll-like receptor 2 (TLR2) and inducible nitric oxide synthase (iNOS) in the development of hepatopulmonary syndrome (HPS). Methods Seventy-one patients were divided into 3 groups: end-stage liver disease with HPS (HPS group, n=31), end-stage liver disease without HPS (non-HPS group, n=30) and healthy volunteers (n= 10). Blood was collected at pre-OLT and Days 3, 7, 14, 21 and 28 post-OLT to detect the plasma LPS level, TLR2mRNA and iNOSmRNA in peripheral blood monecytes. Results The LPS, TLR2mRNA and iNOSmRNA at pre-OLT in HPS group were 4.31±3. 267 ng/L, 336 594.10±366 901.14 and 63 982. 24 ±74 127.47 copies/μg RNA respectively; 1.62±1.34 ng/L, 336 321.53±222 317.17 and 44 169.9±24 993.00 copies/μg RNA respectively in non-HPS group and 0.94±69 ng/L, 10 338.28±3 814.64 and 19 168.49±2 417.35 copios/μgRNA in normal control group. LIS, TLR2mRNA and iNOSmRNA at pre-OLT in HPS group were higher than those in non-HPS group without significance (P0.05), but significantly higher than those in control group (P<0.05). The TLR2mRNA decreased in all end-stage liver disease patients at post-OLT with the improvement of liver function and oxygenation. Conclusion The dysfunction of intestinal barrier and intestinal endotoxemia may be the important mechanisms of HPS through the elevation of LPS level and the expressions of TLR2mRNA and iNOSmRNA.