万胜化风丹对大鼠肝脏CYP450酶系亚型基因的影响

Effects of Wansheng Huafeng Dan on mRNA expression of hepatic cytochrome P450 in rats

目的:研究万胜化风丹(WSHFD)和氯化汞对大鼠肝脏组织细胞色素P450酶系亚型基因的影响。方法:雄性SD大鼠25只,随机分为5组,每组5只,分别为空白组,WSHFD0组(不含朱砂、雄黄的万胜化风丹配方,剂量1.0 g/kg),WSHFD2组(减量2/3朱砂雄黄的万胜化风丹现代配方,剂量1.0 g/kg),WSHFD3组(万胜化风丹古方组,剂量1.0 g/kg),氯化汞组(剂量10mg/kg)。连续灌胃给药7 d后麻醉,取大鼠肝脏组织提取RNA,采用real time RT-PCR检测CYP450酶系亚型基因的表达。结果:与空白组相比,WSHFD0、WSHFD2、WSHFD3对Cyp1a1、Cyp2e1、Cyp3a1、Cyp4a10无明显影响,氯化汞则明显降低其表达(P<0.05);WSHFD0组大鼠肝脏Cyp2b1明显增加,有统计学意义(P<0.05),WSHFD2和WSHFD3则无明显影响,氯化汞组则明显下降,有统计学意义(P<0.05);WSHFD0、WSHFD2、WSHFD3明显增加Cyp3a2、Cyp7a1 mRNA的表达(P<0.05),氯化汞组则无明显影响。结论:(1)万胜化风丹虽含汞,但其对CYP450酶系基因亚型基因的影响与氯化汞不同;(2)WSHFD0、WSHFD2、WSHFD3对P450酶基因的表达无明显差异;表明在万胜化风丹中减量或者去掉朱砂对CYP450酶基因的影响不大;(3)万胜化风丹可明显升高Cyp3a2的基因表达,提示对药物代谢存在潜在的影响;(4)万胜化风丹明显增加Cyp7a1基因的表达,提示其可能影响胆汁酸的代谢。

Objective： To investigate the effects of Wansheng Huafeng Dan （WSHFD） and HgC12 on the expression of cytochrome P450 mRNA in SD rat liver. Method： A total of 25 SD male rats were randomly divided into 5 groups including the control group （ distilled water）, WSHFDO group （ 1.0 g/Kg）, WSHFD2 group （ 1.0 g/Kg）, WSHFD3 group （ 1.0 g/Kg） and HgC12 group （ 10 mg/Kg）. Rats were orally administered with drugs for consecutive 7 days. The expression of CYP450 mRNA was detected by real time quantitative RT-PCR. Results： Compared with the control group, there were no obvious changes of the Cyp1a1, Cyp2e1, Cyp3a1, and Cyp4a10 expression in WSHFDO, WSHFD2 and WSHFD3 groups, but significantly reduced in the HgCl2 group （P 〈 0. 05）. The expression of Cyp3a2 and Cyp7a1 was decreased in WSHFDO, WSHFD2 and WSHFD3 groups （P 〈 0. 05）, but it was unaltered in HgCl2 group. Conclusion： （ 1 ） The effects of WSHFD on Cyp1a1, Cyp2e1, Cyp3a1, Cyp3a2, Cyp4a10 and Cyp7a1 mRNA expression were different from the HgCl2 group; （2） The effects of WSHFD0, WSHFD2 and WSHFD3 on Cyp1a1, Cyp2e1,Cyp3a1, Cyp3a2, Cyp4a10 and Cyp7a1 mRNA expression were not obvious; （3） WSHFD obviously increased the expression of Cyp3a2 mRNA, suggesting it could have potential influence on the drug metabolism ; （4） WSHFD obviously increased the expression of Cyp7a1 mRNA, which suggests it may affect the metabolism of bile acid.