摘要
目的探讨微小RNA(miRNA)-122与抗结核药物性肝损伤的关系,为寻找抗结核药物性肝损伤的早期诊断标志物提供实验依据。方法昆明小鼠异烟肼(INH)组每日1次ig给予2 mL INH(90 mg·kg-1),分别在连续给药1,3,5,7,14,21和28 d后留取小鼠的血清和肝组织标本。采用全自动生化分析仪检测血清谷丙转氨酶(GPT)和谷草转氨酶(GOT)活性,生化法检测肝组织铜锌超氧化物歧化酶(Cu/Zn-SOD)活性和丙二醛(MDA)含量,实时荧光定量PCR检测肝组织中miRNA-122表达。结果药物处理后GPT和GOT呈上升趋势,分别在14和21 d后明显增加(P<0.05);Cu/Zn-SOD和MDA分别在5 d后呈下降趋势和上升趋势(P<0.05)。给药后miRNA-122呈整体下降趋势,给药3 d后miRNA-122下降明显(P<0.05),并在14 d下降到最小值0.58±0.02。相关性分析结果显示,miRNA-122和GPT,Cu/Zn-SOD,MDA存在相关性,相关系数分别为-0.370,0.268和-0.298。结论 miRNA-122与INH所致抗结核药物性肝损伤的发生相关,且可作为INH所致抗结核药物性肝损伤的早期诊断标志物。
OBJECTlVE To study the relationship between microRNA（miRNA）-122 and Iiver injury in-duced by anti-tuberculosis drugs,and to discover the new biomarkers for early diagnosis of this type of Iiver injury. METHODS mice were given 2 mL isoniazid oralIy at 90 mg·kg-1 . BIood and Iiver tissue sampIes were collected at 1,3,5,7,14,21 and 28 d after administration of isoniazid. Serum gIutamic-pyruvic transaminase（ GPT）and gIutamic-oxaloacetic transaminase（ GOT）Ievels were determined using an automatic biochemical analyzer. Cu/ Zn-superoxide dismutase（ Cu/ Zn-SOD ） activity and malondialdehyde（ mDA）content were detected by biochemical method. Real-time qPCR was used to measure the expression of miRNA-122. RESULTS GPT and GOT Ievels were significantIy higher at 14 and 21 d（P﹤0.05）than in the control. Cu/ Zn-SOD began to decIine while mDA began to increase after 5 d（P﹤0.05）. miRNA-122,which progressively decreased after administration,was reduced to the mini-mum 0.58 ±0.02 at 14 d. There were good correlations between miRNA-122 and GPT,Cu/ Zn-SOD, mDA（the correlation coefficients were -0.370,0.268,and -0.298,respectively）,but no correlation with GOT was observed. CONCLUSlON The tissue miRNA-122 profile can be used as a sensitive marker for anti-tuberculosis drug-induced Iiver injury,which could contribute to the early diagnosis of Iiver injury.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2014年第4期569-574,共6页
Chinese Journal of Pharmacology and Toxicology
基金
唐山市重点实验室项目(08150201A-1-8)~~
