肝细胞癌相关胆汁酸代谢失衡及调控机制的研究进展

Research advances in hepatocellular carcinoma-related imbalance of bile acid metabolism and related regulatory mechanism

胆汁酸代谢、肠道菌群及胆汁酸受体调控通路均参与了肝细胞癌(HCC)发生发展的全过程。HCC小鼠模型的肝脏组织、HCC患者的血浆和粪便中某些胆汁酸如甘氨胆酸、牛磺胆酸、牛磺鹅去氧胆酸等水平均显著升高;肠道产胆盐水解酶细菌及梭状芽胞杆菌丰度失衡导致的胆汁酸代谢及机体免疫微环境的改变等也会促进HCC发生;此外,胆汁酸受体如法尼醇X受体、G蛋白偶联受体1、孕烷X受体、本构雄烷受体及鞘氨醇-1-磷酸受体2等多种受体亦被证实可以通过多种途径参与调控HCC的发生发展。胆汁酸代谢的各个环节在HCC的进程中发挥着不同的作用,系统诠释它们之间的相互作用有助于加深对HCC发病机制的认识,开发早期诊断、预后预测及精准治疗的生物靶标。

Bile acid metabolism,gut microbiota,and bile acid receptors are involved in the development and progression of hepatocellular carcinoma(HCC).There are substantial increases in the levels of some bile acids,such as glycocholic acid,taurocholic acid,and taurochenodeoxycholic acid,in the liver tissue of HCC mice and the serum and feces of HCC patients.Bile acid metabolism due to the imbalance of the abundance of bacteria producing bile salt hydrolases and Clostridium in the intestine and the change in immune microenvironment may also promote the development of HCC.Moreover,some bile acid receptors,such as farnesoid X receptor,G protein-coupled bile acid receptor 1,pregnane X receptor,constitutive androstane receptor,and sphingosine-1-phosphate receptor 2,have been shown to participate in the development and progression of HCC through various pathways.Each link of bile acid metabolism plays a different role in the progression of HCC,and a systematic elaboration of the interaction between these links may help to deepen the understanding of the pathogenesis of HCC and develop the biological targets for early diagnosis,prognosis prediction,and precise treatment.