朱砂安神丸、朱砂、硫化汞、氯化汞、甲基汞对小鼠肾转运体基因表达的影响

目的:探讨朱砂安神丸、朱砂、硫化汞(Hg S)、氯化汞(Hg Cl2)和甲基汞(Me Hg)对小鼠肾转运体基因表达的影响。方法:将健康雄性小鼠分别ig等量生理盐水、朱砂安神丸1.8 g·kg-1(含汞0.17 g·kg-1)、朱砂0.2 g·kg-1(含汞0.17 g·kg-1)、高剂量朱砂2 g·kg-1(含汞1.7 g·kg-1)、Hg S 0.2 g·kg-1(含汞0.17 g·kg-1)、Hg Cl20.032 g·kg-1(含汞0.024 g·kg-1)、Me Hg 0.026 g·kg-1(含汞0.024 g·kg-1),每天1次,连续30 d,记录小鼠体重变化。30 d后处死取肾脏,双道原子荧光光度法检测小鼠肾组织汞蓄积量,RT-PCR方法检测小鼠肾组织有机阴离子转运体基因(Oat1,Oat3,Oat2)、多药耐药相关蛋白基因(Mrp2,Mrp4)、尿酸转运体基因(Urat1)的表达。结果:与正常组相比,Hg Cl2组和Me Hg组小鼠肾汞蓄积量显著升高(P<0.05),其余各组肾汞蓄积量与正常组无显著差异;Hg Cl2组和Me Hg组Oat1,Oat2表达显著降低(P<0.05);Me Hg组Mrp2基因的表达显著升高(P<0.05);Hg Cl2组和Me Hg组Mrp4基因表达显著升高(P<0.05);Me Hg组Urat1基因表达显著降低(P<0.05)。结论:Hg Cl2组和Me Hg组小鼠肾汞蓄积量、肾转运体基因表达与正常组有显著差异,其余各组各项检测指标与正常组小鼠相比无显著差异。与Hg Cl2和Me Hg相比,朱砂及其复方对小鼠造成的肾毒性相对较低。

Effect of Zhusha Anshen pill, cinnabar, HgS, HgCl2 and MeHg on gene expression of renal transporters in mice

Objective: To study the effect of Zhusha Anshen pill, cinnabar, HgS, HgCl₂ and MeHg on the gene expression of renal transporters in mice. Method: Healthy male mice were given equivalent physiological saline, Zhusha Anshen pill (1.8 g·kg^-1, containing 0.17 g·kg^-1 of mercury), cinnabar (0.2 g·kg^-1, containing 1.7 g·kg^-1 of mercury), high dose cinnabar (2 g·kg^-1, containing 1.7 g·kg^-1 of mercury), HgS (0.2 g·kg^-1, containing 0.17 g·kg^-1 of mercury), HgCl₂ (0.032 g·kg^-1, containing 0.024 g·kg^-1 of mercury), MeHg(0.026 g·kg^-1, containing 0.024 g·kg^-1 of mercury), once daily, for 30 d, measuring body mass gain. 30 days later, the mice were sacrificed. The mercury accumulation in kidneys was detected with atomic fluorescence spectrometer. Expressions of Oat1,Oat2, Oat3, Mrp2, Mrp4,Urat1 were detected with RT-PCR. Result: Compared with the normal control group, a significant accumulation of Hg in kidney in HgCl₂ and MeHg groups was observed (P<0.05), but these changes were not found in other groups. Compared with normal control group, mRNA expressions of Oat1 and Oat2 were evidently lower in HgCl₂ and MeHg groups, but mRNA expressions of Mrp2 were apparently higher in HgCl₂ group (P<0.05), mRNA expression of Mrp4 was significant higher in HgCl₂ and MeHg groups, and mRNA expression of Urat1 was apparently lower in MeHg group. Conclusion: HgCl₂ and MeHg groups show significant difference from the normal group in mercury accumulation in kidneys and gene expression of kidney transporters, but with no difference between other groups and the normal group. Compared with HgCl₂ and MeHg, cinnabar and its compounds could cause lower renal toxicity to mice.