肠道菌群介导药物性肝损伤的研究进展

药物性肝损伤是临床上最常见、最严重的不良反应之一,既增加患者的医疗负担,也给新药研发及上市带来挑战。目前,药物性肝损伤的发生机制仍不十分明确。近年来,研究发现肠道菌群与药物性肝损伤密切相关,但对肠道菌群参与药物性肝损伤的具体作用机制仍尚无统一结论。肠道菌群可能通过增加肠道通透性致使内毒素外漏、破坏肠道代谢物平衡、直接影响药物代谢及促进炎症和氧化应激等途径参与药物性肝损伤。本文将对肠道菌群参与药物性肝损伤的可能机制,及基于机制的防治措施等研究进展进行综述,以期为药物性肝损伤研究及临床安全合理用药提供科学参考。

Research progress in intestinal microbiota-mediated drug-induced liver injury

Drug-induced liver injury(DILI) is one of the most common and serious clinical adverse reactions, which not only increases the medical burden of patients, but also challenges the development and marketing of new drugs. At present, the occurrence mechanism of DILI is still unclear. Recent researches have shown that DILI is directly related to the intestinal microbiota, but there is no unified conclusion on the specific mechanism of intestinal microbiota participating in DILI. Intestinal microbiota may participate in DILI by increasing intestinal permeability resulting in lipopolysaccharide leakage, destroying the balance of intestinal metabolites, directly affecting drug metabolism, and promoting inflammation and oxidative stress. This paper reviewed the possible mechanisms of intestinal microbiota involved in DILI, and the mechanism-based prevention measures, in order to provide scientific reference for the research on DILI and clinical safe and reasonable drug use.