姜黄素对抗结核药物致肝损伤的抑制作用
曾峥1 张可锋2 李波2 钟明利2
1. 桂林医学院附属医院 2. 桂林医学院药物研究所
摘要：目的：探究姜黄素对抗结核药物致肝损伤（ATLI）的抑制作用。方法：随机将小鼠分为6组，正常组，模型组，姜黄素高、中、低剂量组，阳性对照水飞蓟素组。模型组和各给药组采用异烟肼和利福平灌胃造模，1次/d。8周后，取肝组织标本进行病理组织学检查；采集血样本检测血清谷丙氨酸转氨酶（ALT）、门冬氨酸转氨酶（AST）、丙二醛（MDA）、碱性磷酸酶（AKP）、总胆汁酸（TBA）以及总胆红素（TBIL）;ELISA法检测肝组织匀浆上清液中肿瘤坏死因子α（TNF-α）、白介素-1β（IL-1β）和白介素-6（IL-6）的含量；Western blot检测TLR4,Myd88和NF-κB的表达。结果：姜黄素可明显减轻抗结核药物致小鼠的肝组织损害；姜黄素组ALT、AST、MDA、AKP活性降低，TBIL、TBA含量下降，TNF-α、IL-1β和IL-6水平降低，TLR4、Myd88、NF-κB蛋白表达下调（P＜0.05）。结论：姜黄素能够有效减轻抗结核药物所致的小鼠肝损伤，其作用机理可能与其抗炎和抑制TLR4/Myd88/NF-κB信号通路相关。
关键词：姜黄素;抗结核药物;药物性肝损伤;TLR4/Myd88/NF-κB信号通路;
Inhibitory effect of curcumin on antituberculous drugs induced liver injury
ZENG Zheng1②,ZHANG Kefeng2,LI Bo2,ZHONG Mingli2③.(1. The Affiliated Hospital of Guilin Medical University,Guilin 541001;2. Institute of pharmacology,Guilin Medical University,Guilin 541199,China)
Abstract Objective: To investigate the inhibitory effect of curcumin on anti-tuberculosis drugs induced liver injury(ATLI). Methods: The mice were randomized into six groups: normal group, model group, curcumin high-dose, medium-dose and low-dose groups, and positive control silymarin group. Model group and each medication administration group were given isoniazid and rifampicin intragastric model, once a day. Liver tissue samples were collected for histopathological examination after eight weeks; blood samples were collected to detect serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde(MDA), alkaline phosphatase(AKP), total bile acid(TBA) and total bilirubin(TBIL); ELISA was used to detect the content of tumor necrosis factor α(TNF-α) in supernatant of liver tissue homogenate, interleukin-1β(IL-1β), and interleukin 6(IL-6); and Western blot was used to detect the protein expression of TLR4, Myd88 and NF-κB in liver tissues. Results: Anti-tuberculosis drugs induced liver injury in mice can be significantly alleviated by curcumin, inhibit the activities of ALT, AST, MDA, AKP in curcumin group; content of TBIL and TBA was decreased; levels of TNF-α, IL-1β and IL-6 were decreased too; and expressions of TLR4, Myd88 and NF-κB protein were down-regulated (P<0.05). Conclusion: Curcumin can effectively relieve ATLI, whose action mechanism may be related to antiinflammatory and the regulation of TLR4 / Myd88 / NF-κB pathway.
Keywords: curcumin; antituberculous drugs; drug-induced liver injury; TLR4 / Myd88 / NF-κB signal pathway
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