胆汁酸代谢改变对肝癌发生影响机制的研究

摘要

目的 探讨胆汁酸(bile acids,BAs)各组分在乙型肝炎(乙肝)相关性肝细胞癌(hepatocellur carcinoma,HCC)患者血浆中的浓度及组成比例变化,进一步探索其与HCC的关系.方法 用液相色谱-质谱联用手段分别检测24例HCC患者、15例乙肝肝硬化患者、6例慢性乙肝患者及12例健康对照者血浆中的各BAs组分的变化.用实时荧光定量PCR与免疫组织化学法检测15例肝癌组织与癌旁组织中IL-1β 的表达水平.结果 在24例HCC患者中,BAs组分胆酸、鹅脱氧胆酸、牛磺脱氧胆酸、石胆酸、甘氨鹅脱氧胆酸、甘氨脱氧胆酸相比乙肝肝硬化与健康对照组有明显升高,差异均有统计学意义(P均<0.05),其中石胆酸浓度在不同临床分期患者中差异有统计学意义,C期明显高于B期和A期.癌组织中IL-1β 的表达水平低于癌旁组织.结论 血浆胆汁酸中石胆酸的浓度增高与肝癌进展相关,有可能成为HCC进展的评价指标.%Objective To investigate the changes of serum bile acids (BAs) concentration and components in patients with HBV related hepatocellur carcinoma (HCC), and explore the relationship between BAs and HCC. Methods Liquid chromatography mass spectrometry was used to detect the concentration of serum BAs in 24 HCC patients, 15 HBV related liver cirrhosis patients, 6 chronic HBV hepatitis patients and 12 healthy controls. The expression levels of IL-1β in liver tissues and paracancer tissue were detected by real-time PCR and immunohistochemistry in 15 liver cirrhosis cases. Results The cholic acid, chenodeoxycholic acid, tauro ursodesoxy cholic acid, lithocholic acid, glycochenodeoxycholic acid, glycochenodeoxycholic acid concentrations were significantly higher in 24 HCC patients than those in the heath control and liver cirrhosis group (P < 0.05). The concentrations of lithocholic acid (LCA) were positively correlated with the clinical stage of HCC and showed significant differences in different stages, the concentration at stage C was obviously higher than that at stage B and stage A. The expression level of IL-1β in cancer tissues was lower than that in adjacent tissues.Conclusions The increase of plasma bile acid LCA is correlated with the development of liver cancer. It may be an evaluation index for the progress of HCC.