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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,以及有一定的降低肝切除暴发性肝衰竭死亡率作用
OBJECTIVE: To investigate the effects of hepatic microsomal drug metabolizing enzymes (hepatic drugs) inducing agents such as phenobarbital (PB) and rifampin (RFP) on liver enzymes and liver failure. Methods: The effects of PB and RFP on cytochrome P450 (P450), cytochrome b5 (Cyt.b5), aniline hydroxylase activity, hepatectomy-induced hepatic failure mortality and hyperhemamine hepatic coma survival Impact of the period. Results: PB and RFP could significantly improve the content of liver P450 and the activity of aniline hydroxylase after normal liver and partial hepatectomy. Within 5 h to 9 d after hepatectomy, mortality from fulminant hepatic failure in PB-treated mice was 32.1% and 49.2%, respectively, lower than that in the blank control group. The survival time was significantly longer than that of the blank control group (160.7 ± 84.1) h and (128.9 ± 92.6) h, respectively. In addition, in hepatectomy mice, hyperhemamine hepatic coma survival induced by NH4Cl in PB and RFP groups was (60.8 ± 22.5) h and (112.9 ± 7.2) h, respectively, which was also significantly longer than that in the blank control group (44.6 ± 28.3) h. CONCLUSION: PB and RFP can significantly induce liver enzymes, prolong the survival of hyperhemaminemic hepatic coma, as well as reduce the mortality of hepatic failure caused by hepatectomy