肝药酶诱导剂对暴发性肝衰竭的影响

EFFECT OF MICROSOMAL DRUG METABOLIZING ENZYME INDUCERS ON FULMINANT ILVER FAILURE

目的:研究肝微粒体药物代谢酶(肝药酶)诱导剂苯巴比妥(PB)和利福平(RFP)对肝药酶和肝衰竭的影响。方法:观察PB和RFP对肝药酶细胞色素P450(P450)和细胞色素b5(Cyt.b5)的含量、苯胺羟化酶活性、肝切除暴发性肝衰竭死亡率和高血氨性肝昏迷存活期的影响。结果:PB和RFP能明显提高正常肝脏和部分肝切除后再生肝P450含量和苯胺羟化酶活性。在肝切除术后5h至9d内,经PB处置的小鼠暴发性肝衰竭死亡率低于空白对照组,分别为32.1%和49.2%。存活期也明显长于空白对照组,分别为(160.7±84.1)h和(128.9±92.6)h。此外,在肝切除小鼠中,PB和RFP组NH4Cl所致的高血氨性肝昏迷存活期分别为(60.8±22.5)h和(112.9±7.2)h,也明显长于空白对照组的(44.6±28.3)h。结论:PB和RFP能显著地诱导肝药酶,延长高血氨性肝昏迷的存活期。

Objective:To study the effect of hepatic microsomal drug-metabolizing enzyme inducers rifampin (RFP) and phenobarbital (PB) on fulminant liver failure Methods:The effects of PB and RFP on the contents of microsomal drug metabolizing enzyme cytochrome P450(P450) and cytochrome b 5(Cyt b 5),the activity of aniline hydroxylase,the mortality of fulminant liver failure caused by hepatectomy,and the survival period of ammonemia hepatic coma induced by ammonium chloride were investigated Results:The content of P450 and the activity of aniline hydroxylase were significantly increased in the normal liver and regenerated liver after partial hepatetomy by the treatment with PB and RFP The mortality of fulminant liver failure by hepatetomy was 32 1% in mice treated with PB,compared to 49 2% in control within 5h to 9d after the hepatetomy The survival period was longer in PB group than in control,(160 7±84 1)h and (128 9±92 6)h,respectively In addition,the survival periods of ammonemia hepatic coma induced by NH4Cl in the groups treated with both PB and RFP were (60 8±22 5)h and (112 9±7 2)h,respectively,which were longer than that in control (44 6±28 3)h following the hepatetomy Conclusion:PB and RFP could significantly induce microsomal drug metabolizing enzyme and extend the survival period of ammonemia hepatic coma,and also decrease the mortality of fulminant liver failure by hepatetomy to some extent