姜黄素对抗结核药物致肝损伤的抑制作用  

Inhibitory effect of curcumin on antituberculous drugs induced liver injury

作　　者：曾峥[1] 张可锋[2] 李波[2] 钟明利[2] ZENG Zheng;ZHANG Kefeng;LI Bo;ZHONG Mingli(The Affiliated Hospital of Guilin Medical University,Guilin 541001;Institute of pharmacology,Guilin Medical University,Guilin 541199,China)

机构地区：[1]桂林医学院附属医院,广西桂林541001 [2]桂林医学院药物研究所,广西桂林541199

出　　处：《华夏医学》2022年第4期1-5,共5页Acta Medicinae Sinica

基　　金：国家自然科学基金项目(81660104);广西自然科学基金项目(2020JJB140061);桂医中青年教职工科研能力提升项目(2018glmcy067);广西高校中青年教师基础能力提升项目(2017KY0483)。

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。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 anti-inflammatory and the regulation of TLR4/Myd88/NF-κB pathway.

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 

分 类 号：R285.5[医药卫生—中药学]