与抗结核药物肝损伤易感性相关的基因多态性研究进展

Research Advances in Genetic Polymorphisms Associated with Susceptibility to Anti-Tuberculosis Drug Induced Liver Injury

抗结核药物联合治疗引起的抗结核药物肝损伤(AT-DILI)影响着患者疗效和健康。遗传因素可影响药物代谢过程中相关蛋白质的表达水平,从而导致AT-DILI的发生。这些AT-DILI易感性相关蛋白可作用于药物代谢过程(与Ⅰ相代谢酶、Ⅱ相代谢酶的活性均有密切关系),代谢物质积聚过程(影响着胆汁酸、脂肪酸和含铁血黄素的积聚),免疫反应过程(影响多种免疫因子的功能与表达)及氧化应激过程(影响氧化因子的表达及相关氧化反应的信号通路)。未来,对遗传多态性的研究有望发现AT-DILI敏感人群,从而有针对性地预防AT-DILI的发生和进展。

Combined anti-tuberculosis drugs generated anti-tuberculosis drug induced liver injury( AT-DILI) affects the therapeutic efficacy and health of the patients. Genetic factors can affect the expression levels of related proteins in the process of drug metabolism,which leads to the occurrence of AT-DILI. These AT-DILI susceptibility-related proteins act on the drug metabolism process( closely related to the activities of phase Ⅰ and phase Ⅱ metabolizing enzymes),the accumulation of metabolites( affecting the accumulation of bile acids,fatty acids and hemosiderin),the process of immune stress( affecting the function and expression of various immune factors),and the process of oxidative stress( signal pathway affecting the expression of oxidative factors and related oxidation reactions). In the future,research on genetic polymorphism is expected to find AT-DILI sensitive populations,so as to targetedly prevent the occurrence and progress of AT-DILI.