2022 年第 10 期 第 17 卷

全反式维甲酸通过脂代谢途径抗丙型肝炎相关肝癌的研究进展

Research progress of all-trans retinoic acid treating hepatitis C associated hepatocellular carcinoma through the lipid metabolism pathway

作者：赵晗雪孔璐

英文作者：Zhao Hanxue Kong Lu

单位：首都医科大学基础医学院，北京100069

英文单位：School of Basic Medical Sciences Capital Medical University Beijing 100069 China

关键词：全反式维甲酸；丙型肝炎病毒；肝癌；脂代谢

英文关键词：All-transretinoicacid;HepatitisCvirus;Hepatocellularcarcinoma;Lipidmetabolism

• 摘要：

• 丙型肝炎病毒（HCV）作为肝癌的主要危险因素之一，其复制、组装和感染均可以引起宿主肝细胞内过量脂滴累积。脂滴内三酰甘油等中性脂的代谢产物可破坏细胞稳态，导致细胞变性坏死，推动肝硬化进程。直接抗病毒药物（DAA）尽管已在临床广泛应用，但在国内仍无统一的一线治疗方案。且有数据表明，接受DAA治疗的患者，其肝癌复发率较未接受者更高。近期研究发现全反式维甲酸（ATRA）具有抗HCV及其相关肝癌的作用，可能的机制为ATRA抑制宿主感染肝细胞的脂肪合成、促进脂肪干细胞分化，缓解感染肝细胞的脂变性，进而终止肝硬化的进程，从而起到抗癌的作用。本文主要对HCV感染与肝癌发生发展的脂代谢机制以及ATRA抗癌及缓解脂代谢紊乱的主要信号分子和通路进行综述。

• As one of the major risk factors for hepatocellular carcinoma (HCC), hepatitis C virus (HCV), its replication, assembly and infection can cause the accumulation of lipid droplets in host hepatocytes. The metabolites of triglyceride and other neutral lipids in lipid droplets can destroy cell homeostasis, lead to cell degeneration and necrosis, and promote the process of liver hardness. Although direct acting antiviral agents (DAA) have been widely used in clinical practice, there is still no first-line treatment in China. Moreover, data shows that the HCC recurrence rate in patients receiving DAA is higher than that of non-recipients. Recently, studies have found that all-trans retinoic acid (ATRA) have the effect of anti-HCV related HCC. The possible mechanism may be that ATRA inhibits the lipid synthesis in host infected hepatocytes, promote adipose stem cell differentiation, and alleviate lipid degeneration in infected hepatocytes alleviates the fatty degeneration of infected hepatocytes, thus  terminating the process of liver cirrhosis as an anti-cancer role. This paper mainly reviews the lipid metabolism mechanism of HCV infection and hepatocarcinogenesis and development, as well as the main signaling molecules and pathways of ATRA for anti-cancer and alleviation of lipid metabolism disorder.