原代肝细胞体外培养用于利福平和异烟肼肝毒性的研究

目的:研究利福平(rifampicin,LFP)和异烟肼(isoniazid,INH)对体外大鼠肝细胞的毒性.方法:以乳酸脱氢酶(LDH)释放量反映肝细胞损伤,以尿素分泌量和大鼠白蛋白合成量反映肝功能.结果与结论:15 mg/mL异烟肼(5 mL)、10 mg/mL利福平(5 mL)以及相同剂量两药合用时LDH释放量分别为对照组的1.3倍、1.5倍和1.6倍,产生的白蛋白量分别为不加药时的25%、28%和28%,尿素产量也有相应下降但程度不如白蛋白显著.说明该剂量的利福平和异烟肼对大鼠肝细胞均有毒性作用,但两药合用并不增加毒性.进一步将此原代肝细胞模型与连续细胞系小鼠成纤维细胞株L929、与文献报道的动物模型比较,探索原代肝细胞模型在肝毒性研究中应用的可行性.

Studies on Rifampicin and Isoniazid-induced Hepatotoxicity Using in vitro Primary Hepatocytes

AIM:In vitro rat hepatocytes were used to study isoniazid and rifampicin induced hepatotoxicity.METHODS:The level of lactate dehydrogenase (LDH) leakage was selected as an indicator for hepatocytes viability while both albumin biosynthesis and ureagenesis were used as indicators for liver-specific functions.RESULTS AND CONCLUSION:It was found that the LDH leakage of hepatocytes exposed to 5 mL of 10 mg/mL rifampicin,5 mL of 15 mg/mL isoniazid and their combination of both drugs increased by 30%,50% and 60% in comparison to the control group,respectively.On the other hand,the corresponding albumin production decreased to 25%,28% and 28% of that in the control group,respectively.Ureagenesis also decreased but the change was not so significant as that of LDH leakage and albumin production.The observations showed that either rifampicin or isoniazid caused hepatotoxicity.However,the combination of both drugs did not further worsen the hepatotoxicity.The results suggested that it is necessary to compare the exploited in vitro rat primary hepatocytes with mouse fibroblast cell line (L929) and the cited animal models as well as to explore the feasibility of application of in vitro primary hepatocytes in hepatotoxicity studies in the future.