利福平、异烟肼合用与单用时的肝毒性比较

Comparison of Hepatotoxicity Induced by Isoniazid,Rifampicin or Isoniazid and Combined with Rifampicin

目的:探讨异烟肼(INH)与利福平(RFP)合用致肝毒性增加的部分作用机制。方法:采用在体心脏灌流法获取小鼠原代肝细胞,将其常规培养72h后,含INH(87.5μmol/L)、RFP(48.6μmol/L)、INH+RFP(87.5μmol/L+48.6μmol/L)培养液培养48h后,常规HE染色,光镜下观察肝细胞生长情况并计数。结果:INH与RFP合用后与INH单用时比较肝细胞计数减少(P<0.05,P<0.01)。结论:RFP和INH合用后使INH肝毒性代谢物浓度增加,可能是其肝毒性增加的原因之一。

Objective： To investigate the mechanism of the effect of Isoniazid （INH）and Rifampicin （RFP）. Methods： The mouse hepatocytes were obtained through the Cardio-perfusion in mouse. Mouse hepatocytes were isolated by two-step in situ collagenase perfusion methods,72 hours after culture of mouse hepatocytes were cultivated, the culture liquid with INH （87.5 μmol/L）, RFP（48.6 μmol/L） , INH ＋ RFP（87.5 μmol/L ＋ 48.6 μmol/L）were cultivated for 48 hours,routine HE dyeing and growth of hepatocytes were observed and counted under electromicroscope. Results： Hepatotoxicity of INH was lower when Combined with RFP than with INF alone （ P 〈 0.05, P 〈 0. 01 ）. Conclusion：RFP can increase the concentration of Acetylhydrazin （AHZ）and Hydrazine, which may increase the hepatotoxicity of INH.