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双歧杆菌对慢性肝病的干预作用及其机制
DOI: 10.12449/JCH260230
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：潘李轶负责文献检索，撰写文章；陈玉、黄钰雯、裴浩、吴凤兰、叶绿萍、王娜协助文献检索；陈月桥负责修改和审校文章。
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摘要: 相较于传统慢性肝病（CLD）治疗方法，双歧杆菌具有干预靶点多、生物安全性高和宿主相容性好等特性，为干预CLD进展提供了微生态调控新策略。多项研究表明，双歧杆菌通过调节肠道菌群、保持抗氧化、促进能量消耗、减轻炎症、改善糖脂代谢和抗肿瘤等多个方面，调节肝脏稳态及治疗CLD。本文系统综述了国内外关于双歧杆菌治疗CLD的相关研究，探讨其不同作用机制，并对涉及的核转录因子红系2相关因子2和AMP活化的蛋白质激酶等相关信号通路与肝脏的交互作用进行阐述，以期为益生菌干预CLD病理提供依据，为CLD的综合治疗提供新思路。Abstract: Compared with traditional therapies for chronic liver disease （CLD）， Bifidobacterium has the characteristics of multi-target intervention， high biosafety， and good host compatibility and provides new strategies for intervention of CLD progression in terms of microecological regulation. Various studies have shown that Bifidobacterium regulates liver homeostasis and exerts a therapeutic effect on CLD by regulating intestinal flora， maintaining antioxidation， promoting energy consumption， alleviating inflammation， improving glycolipid metabolism， and exerting an antitumor effect. This article systematically reviews the studies on Bifidobacterium in the treatment of CLD in China and globally， explores their different mechanisms， and elaborates on the interaction between related signaling pathways （such as the nuclear factor erythroid 2-related factor 2 signaling pathway and the adenosine monophosphate-activated protein kinase signaling pathway） and the liver， in order to provide a basis for probiotic intervention in liver pathology， as well as new ideas for the comprehensive treatment of CLD.
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Key words:
- Liver Diseases /
- Bifidobacterium /
- Signal Transduction
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注： CLD，慢性肝病；occludin，闭合蛋白；IGF-1，胰岛素样生长因子1；LPS，脂多糖。
图 1 双歧杆菌通过肠道屏障干预CLD的过程
Figure 1. The process of Bifidobacterium intervening CLD through the intestinal barriers
注： CLD，慢性肝病；PGC-1α，过氧化物酶增殖激活受体-γ共激活因子-1α；Nrf2，核转录因子红系2相关因子2；ARE，抗氧化响应元件；HO-1，血红素加氧酶1；CAT，过氧化氢酶；SOD，超氧化物歧化酶；ROS，活性氧。
图 2 双歧杆菌通过抗氧化和消耗能量干预慢性肝病的过程
Figure 2. The process of Bifidobacterium intervening CLD through antioxidation and energy consumption
注： CLD，慢性肝病；LPS，脂多糖；MD-2，髓样分化蛋白2；TLR4，Toll样受体4；MyD88，髓分化因子88；IRAK，白细胞介素-1受体相关激酶；TRAM，易位关联膜蛋白1；TRIF，血清β干扰素TIR结构域衔接蛋白；TRAF，肿瘤坏死因子受体相关因子；IKK，kappa B 抑制因子激酶；IRF3，干扰素调节因子3；IL-6，白细胞介素-6；TNF-α，肿瘤坏死因子-α。
图 3 双歧杆菌通过相关炎症机制干预慢性肝病的过程
Figure 3. The process of Bifidobacterium intervening CLD through the related inflammatory mechanisms
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