朱砂安神丸、朱砂、硫化汞和氯化汞对大鼠肝脏细胞色素P450酶的影响

Effect of cinnabar,Zhusha Anshenwan,HgS and HgCl_2 on expression of cytochrome P450 in livers of rats

目的探讨硫化汞(HgS)、氯化汞(HgCl2)、朱砂及其复方朱砂安神丸对肝细胞色素P450酶的影响。方法雄性SD大鼠ig给予朱砂安神丸1.4 g.kg-1、朱砂0.15 g.kg-1、HgS 0.15 g.kg-1和HgCl20.02 g.kg-1,每天1次,连续21 d,观察大鼠日常行为变化,记录体质量,末次给药后处死大鼠,检测血清谷丙转氨酶(ALT)、肝指数和肝汞蓄积量;RT-PCR法检测肝金属硫蛋白-2(MT-2),CYP1A1,CYP1A2,CYP3A2,CYP4A10,CYP2B1和结构型雄烷受体(CAR)基因的表达。结果与正常对照组相比,HgCl2组大鼠饮食、活动减少,精神较差,体质量明显降低,肝有增大趋势,肝汞蓄积量明显升高(P<0.05),MT-2,CYP1A1,CYP1A2基因表达明显升高(P<0.05),CYP4A10有增高趋势,CAR基因表达明显降低。与正常对照组相比,朱砂、朱砂安神丸和HgS组的肝指数、ALT和汞蓄积量没有明显差异,同时朱砂安神丸、朱砂和HgS组的MT-2,CYP1A1,CYP1A2,CYP3A2,CYP4A10,CAR及CYP2B1基因表达没有明显变化,但朱砂可明显上调CYP3A2基因表达。结论朱砂安神丸、朱砂和HgS短期给药肝组织汞蓄积量远小于HgCl2,未改变MT-2、CYP酶、CAR基因的表达,但朱砂可上调CYP3A2基因表达,而HgCl2可明显影响MT-2、CYP酶、CAR的基因表达。

OBJECTIVE To explore effect of cinnabar and cinnabar-containing Zhusha Anshenwan on cytochrome P450（CYP） mRNA in liver of rats.METHODS Adult Sprague-Dawley rats were gavaged with Zhusha Anshenwan 1.4 g·kg-1,cinnabar 0.15 g·kg-1,HgS 0.15 g·kg-1,HgCl2 0.02 g·kg-1,once daily,for 21 d,and liver toxicity was determined by measuring body mass gain.Liver index,alanine transaminase（ALT） ativity,mercury accumulation in liver and mRNA levels of metalloehionein-2（MT-2）,CYP1A,CYP3A2,CYP4A10,CYP2B1 and constitute androstane receptor（CAR） genes were detected with RT-PCR.RESULTS Compared with normal control group,body mass gain retarded in HgCl2 group with a reduced food intake and activities.A significant accumulation of Hg in livers in HgCl2 group was evident,however these changes were not evident in cinnabar,Zhusha Anshenwan and HgS groups.Compared with normal control group,mRNA expressions of MT-2,CYP1A1,CYP1A2 were evidently higher and CAR were apparently lower in HgCl2 group.Compared with nromal control group,accumulation of Hg,liver index,ALT,MT-2,CYP1A1,CYP1A2 and CYP4A10 CAR,CYP2B1 mRNA in cinnabar,Zhusha Anshenwan and HgS groups were unaltered,except that CYP3A2 mRNA expression obviously increased in cinnabar group.CONCLUSION Zhusha Anshenwan,cinnabar,and HgS accumulate much less mercury in the liver than HgCl2 at clinical dose for 3 weeks.MT-2,CAR and cytochrome P450 genes are altered in HgCl2 group,CYP3A2 mRNA increase in cinnabar group,but all of above are not changed in Zhusha Anshenwan and HgS groups.