甲醛和甲醇染毒对小鼠造血组织的毒性作用

Exploration of Mechanism of Hematopoietic Toxicity after Formaldehyde and Methanol Exposure in Mice

为了探究甲醛(Formaldehyde,FA)对造血组织的毒性,分析甲醛的毒性是否与中间代谢产物——甲醇(Methanol,MeOH)的毒性一致,以72只昆明小鼠为受试动物,随机分为6组〔1对照组,仅灌服生理盐水;2FA40组,单独灌服甲醛(FA),w(FA)为40 mg/kg;3 MeOH40组,单独灌服甲醇(MeOH),w(MeOH)为40 mg/kg;4FA_(10)+MeOH30组,同时灌服甲醛和甲醇,w(FA)为10mg/kg、w(MeOH)为30 mg/kg;5FA_(20)+MeOH20组,同时灌服甲醛和甲醇,w(FA)为20 mg/kg、w(MeOH)为20 mg/kg;6FA_(30)+MeOH10组〕,同时灌服甲醛和甲醇,w(FA)为30 mg/kg、w(MeOH)为10 mg/kg,连续灌胃7 d,检测小鼠的肝脏氧化损伤程度、血液和骨髓内甲醛含量以及甲醛脱氢酶的相对表达量,比较甲醇和甲醛毒性的差异性.结果表明:与对照组相比,各染毒组小鼠肝脏内ROS(reactive oxygen,活性氧)含量极显著增加(P<0.01),FA_(30)+MeOH10组的ROS含量显著上升(P<0.05);肝脏内MDA(malondialdehyde,丙二醛)含量极显著下降(P<0.01),GSH(glutathione,谷胱甘肽)含量极显著升高(P<0.01);在甲醛和甲醇联合染毒组中,随着甲醛含量的增加和甲醇含量的减少,氧化损伤程度呈上升趋势.AHMT(4-amino-3-hydrazine-5-mercapto-1,2,4-triazole)法测定结果显示,各染毒组小鼠血液和骨髓中甲醛含量与对照组相比均无显著差异;RT-PCR法测定结果显示,各染毒组小鼠中甲醛脱氢酶的相对表达量较对照组显著增加;FA40组与MeOH40组甲醛脱氢酶的相对表达量差异显著(P<0.01);与FA_(30)+MeOH10组相比,FA_(10)+MeOH30组中甲醛脱氢酶的相对表达量极显著增加(P<0.01),甲醛和甲醇联合染毒组中甲醛脱氢酶的相对表达量随着甲醛含量的增加和甲醇含量的减少呈上升趋势.研究显示,甲醛和甲醇的毒性不一致,甲醛对造血组织的毒性可能存在其他方式.

To investigate the mechanism of formaldehyde hematopoietic toxicity,male Kunming mice were randomly divided into 6 groups：（ 1） saline group;（ 2） FA40 group,w（ FA） = 40 mg/kg;（ 3） MeOH40 group,w（ MeOH） = 40 mg/kg;（ 4） FA（10）＋ MeOH30 group,w（ FA） = 10 mg/kg and w（ MeOH） = 30 mg/kg;（ 5） FA（20）＋ MeOH20 group,w（ FA） = 20 mg/kg and w（ MeOH） = 20 mg/kg; and（ 6）FA（30）＋ MeOH10 group,w（ FA） = 30 mg/kg and w（ MeOH） = 10 mg/kg. The test species were administered orally with FA,MeOH and vehicle control for 7 d. Biomarkers of oxidative stress（ ROS,MDA,GSH） in liver,the concentration of formaldehyde in blood and bone marrow,and the expression of glutathione-dependent formaldehyde dehydrogenase（ FDH） in blood and bone marrow were determined.The results showed that compared with the control groups,oxidative damage levels in the FA and methanol groups were dramatically increased. Compared with the FA（10）＋ MeOH30 group,both ROS（ P〈0. 05） and MDA（ P〈0. 01） content decreased significantly in the FA（30）＋ MeOH10 group,while the content of GSH significantly increased（ P〈0. 01）. In the combined exposure group,with the increasing of the concentration of formaldehyde,the oxidative damage rose;4-amino-3-hydrazine-5-mercapto-1,2,4-triazole（ AHMT） assay were used to detect the FA content. The experimental results showed no significant difference of formaldehyde concentration between blood and bone marrow（ P〈0. 05） after treatment.However,the relative expression of formaldehyde dehydrogenasein blood and bone marrow increased significantly（ P〈0. 05） compared with the control group,while it was significantly different with the MeOH40 group and FA40 group. Compared with the FA（30）＋ MeOH10 group,the expression of formaldehyde dehydrogenase in the FA（10）＋MeOH30 group increased significantly（ P〈0. 01）. In the combined exposure groups,formaldehyde dehydrogenase increased as formaldehyde concentration increased. The study showed that the toxicity of formaldehyde and methanol were inconsistent.