CAJ | 학술논문

目的探讨抗结核药对小鼠肝细胞线粒体功能的影响,为减少抗结核药致肝损伤发生提供实验依据.方法 150只昆明种小鼠分成5组,分别为对照组(C组)、利福平(RFP)组、异烟肼(INH)组、吡嗪酰胺(PZA)组以及三种药物的混合组(MIX),分别予0.9％氯化钠溶液0.3 mL/d,RFP 135 mg·kg-1·d-1,INH 90 mg·kg-1·d-1,PZA 315 mg·kg-1·d-1和RFP+ INH+PZA(135+90+315) mg·kg-1·d-1,每天灌胃给药一次,在用药3、7和15 d分批处死小鼠取标本.动态观察各组肝细胞线粒体丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、谷胱甘肽过氧化物酶(GSH-PX)活性和线粒体DNA(mtDNA)中8羟基脱氧鸟苷(8-OH-dG)含量.采用单因素方差分析或秩和检验.结果随着用药时间的延长,RFP组(Z=6.020,P=0.049)、INH组(Z=10.220,P=0.006)和MIX组(Z=7.460,P=0.024) MDA含量逐步增高,RFP组(F=6.751,P=0.011)和MIX组(F=4.891,P=0.041)的SOD活性低于对照组和PZA组,RFP组GSH-PX活性明显减低(F=32.445,P＜0.01),其余各组无明显变化规律.各组8-OH-dG含量随用药时间延长均有升高趋势,其中RFP组(F=6.602,P＜0.01)、PZA组(F=5.927,P＜0.01)和MIX组(F=7.974,P＜0.01)升高明显.结论抗结核药可导致小鼠肝细胞线粒体内MDA和mtDNA中8-OH-dG含量升高,SOD和GSH-PX活性降低.随着用药时间的延长损伤呈加重趋势,三种药物联合用药,可加重对小鼠肝细胞线粒体的损伤程度.
목적 탐토항결핵약대소서간세포선립체공능적영향,위감소항결핵약치간손상발생제공실험의거.방법 150지곤명충소서분성5조,분별위대조조(C조)、리복평(RFP)조、이연정(INH)조、필진선알(PZA)조이급삼충약물적혼합조(MIX),분별여0.9％록화납용액0.3 mL/d,RFP 135 mg·kg-1·d-1,INH 90 mg·kg-1·d-1,PZA 315 mg·kg-1·d-1화RFP+ INH+PZA(135+90+315) mg·kg-1·d-1,매천관위급약일차,재용약3、7화15 d분비처사소서취표본.동태관찰각조간세포선립체병이철(MDA)함량、초양화물기화매(SOD)활성、곡광감태과양화물매(GSH-PX)활성화선립체DNA(mtDNA)중8간기탈양조감(8-OH-dG)함량.채용단인소방차분석혹질화검험.결과 수착용약시간적연장,RFP조(Z=6.020,P=0.049)、INH조(Z=10.220,P=0.006)화MIX조(Z=7.460,P=0.024) MDA함량축보증고,RFP조(F=6.751,P=0.011)화MIX조(F=4.891,P=0.041)적SOD활성저우대조조화PZA조,RFP조GSH-PX활성명현감저(F=32.445,P＜0.01),기여각조무명현변화규률.각조8-OH-dG함량수용약시간연장균유승고추세,기중RFP조(F=6.602,P＜0.01)、PZA조(F=5.927,P＜0.01)화MIX조(F=7.974,P＜0.01)승고명현.결론 항결핵약가도치소서간세포선립체내MDA화mtDNA중8-OH-dG함량승고,SOD화GSH-PX활성강저.수착용약시간적연장손상정가중추세,삼충약물연합용약,가가중대소서간세포선립체적손상정도.
Objective To study the influence of anti-tuberculosis drugs on mitochondrial function in mice hepatocytes and to explore the mechanism of the anti-tuberculosis drugs induced liver injury.Methods A total of 150 mice were randomized into five groups:control group (C group),rifampin (RFP) group,isoniazid (INH) group,pyrazinamide (PZA) group and three antituberculosis drug combination group (MIX).The mice were administered intragastrically with 0.9 ％ NaC1 solution or RFP 135 mg · kg-1 · d-1 or INH 90 mg · kg-1 · d-1 or PZA 315 mg · kg-1 · d-1 or RFP+INH+ PZA (135±90+315) mg · kg-1 · d-1 once a day.Ten mice in each group were sacrificed at day 3,7 and 15 of administration,respectively.The following parameters in each group were monitored.the concentration of malondialdehyde (MDA),the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in mitochondrion of hepatocytes and the concentration of 8-hydroxydeoxyguanosine (8-OH-dG) in mitochondrial DNA (mtDNA).The data were analyzed by one-way ANOVA or rank sum test.Results Along with the prolonged medication duration,the concentrations of MDA all gradually increased in RFP group (Z=6.020,P=0.049),IN H group (Z=10.220,P=0.006) and MIX group (Z=7.460,P=0.024),whereas the activity of SOD significantly decreased in RFP group (F=6.751,P =0.011 ) and MIX groups (F=4.891,P =0.041 ) compared with control group and PZA group.Meanwhile,the activity of GSH-PX was significantly lower in RFP group compared to the other groups (F=32.445,P＜0.01).The changes of other parameters didn't show meaningful trend.The concentrations of 8-OH-dG in mtDNA also increased in all treated groups,and those were all significantly increased in RPF group (F=6.602,P＜0.01 ),PZA group (F=5.927,P＜0.01) and MIX groups (F=7.974,P＜0.01).Conclusions Antituberculosis drugs can induce higher MDA concentration in mitochondrion and higher 8-OH-dG concentration in mtDNA,while result in lower activities of SOD and GSH-PX.The liver damage tends to become more severe along with the prolonged medication duration.The combination of three antituberculosis drugs could aggravate the damage of mitochondrion in mice hepatocytes.