论文部分内容阅读
目的 研究苯巴比妥对双氯芬酸钠毒性和代谢的影响。方法 用夹层细胞培养的方法 ,将双氯芬酸钠暴露于大鼠肝细胞或经苯巴比妥预处理后的肝细胞 ,测定培养液中肝细胞酶渗出量、细胞色素P4 5 0 3A(CYP 3A)活性和双氯芬酸钠代谢产物的含量。结果 肝细胞基础CYP 3A活性随培养时间的延长而逐渐降低 ,CYP 3A的这种下降趋势可被细胞色素P4 5 0诱导剂如苯巴比妥所改变。培养液中乳酸脱氢酶 (LDH) ,丙氨酸转氨酶 (ADLT)和天冬氨酸转氨酶 (AST)水平及双氯芬酸钠代谢产物 4’ -OH -DF和 5 -OH -DF的含量随双氯芬酸钠暴露浓度的增加而增加 ,各暴露组之间以及暴露组与对照组之间未见显著性差异。但肝细胞经苯巴比妥预处理后 ,再暴露于双氯芬酸钠中 ,培养液中 4’ -OH -DF和 5 -OH -DF浓度以及LDH水平均明显增加。结论 随着肝细胞内CYP 3A活性的增强 ,双氯芬酸钠对肝细胞的毒性和在肝细胞中的代谢都会增强
Objective To investigate the effect of phenobarbital on the toxicity and metabolism of diclofenac sodium. Methods Membrane cell culture method was used to expose diclofenac sodium to rat hepatocytes or to hepatocytes pretreated with phenobarbital. The amount of hepatocyte exudative enzyme in the culture fluid was measured. Cytochrome P450 3A (CYP 3A ) Activity and diclofenac sodium metabolites content. Results The basal CYP 3A activity of hepatocytes gradually decreased with the prolongation of culture time. This downward trend of CYP 3A could be changed by the cytochrome P4 50 inducer such as phenobarbital. The levels of lactate dehydrogenase (LDH), alanine aminotransferase (ADLT) and aspartate aminotransferase (AST) and the contents of diclofenac sodium metabolites 4’-OH-DF and 5-OH- There was no significant difference between exposure groups and between exposure groups and control groups. However, after pretreatment of hepatocytes with phenobarbital, they were exposed to diclofenac sodium. The concentration of 4’-OH-DF, 5-OH-DF and LDH in the culture medium were significantly increased. Conclusion With the enhancement of CYP 3A activity in hepatocytes, the toxicity of diclofenac sodium to hepatocytes and the metabolism in hepatocytes will be enhanced