外源性蛋氨酸对饮水砷暴露雌性小鼠体内砷形态分布的影响

目的 探讨外源性蛋氨酸(methionine,Met)对饮水砷暴露小鼠体内不同组织器官砷形态分布的影响.方法 将健康清洁级雌性昆明小鼠40只,随机分为对照组、单纯砷染毒组及低、中、高剂量Met与砷联合染毒组,每组8只.除对照组小鼠饮蒸馏水外,其余各组小鼠以自由饮水方式饮含50mg/L亚砷酸钠的水,连续染毒4周.在染毒的第4周,低、中、高剂量Met与砷联合染毒组小鼠分别被腹腔注射100、200、400 mg/kg的Met溶液,对照组和单纯砷染毒组小鼠被腹腔注射生理盐水,连续注射7 d.末次注射24 h后,处死小鼠,快速取血,分离肝和脑组织,分别检测无机砷(iAs)、一甲基胂酸(MMA)和二甲基胂酸(DMA)含量,并计算各组织中总砷含鼍(TAs)及砷一甲基化率(primary methylation ratio,PMR)和二甲基化率(secondary methylation ratio,SMR).结果 单纯砷染毒组和高、中、低剂量Met与砷联合染毒组小鼠肝、脑组织及全血中iAs、MMA、DMA和TAs含量均高于对照组,差异有统计学意义(P<0.05).与单纯砷染毒组比较,中、高剂量Met与砷联合染毒组小鼠肝组织中DMA含量和PMR较高,差异有统计学意义(P<0.05).与单纯砷染毒组比较,各剂量Met与砷联合染毒组小鼠全血中iAs、MMA和TAs含量均下降,差异有统计学意义(P<0.05).各剂量Met与砷联合染毒组小鼠脑组织中DMA和TAs含量低于单纯砷染毒组,差异有统计学意义(P<0.05).结论 外源性Met 对小鼠体内砷甲基化代谢具有促进作用,并可加速体内砷化物的排泄,从而减少血液和脑组织中的砷负荷.

Effects of Exogenous Methionine on Arsenical Distribution in Female Mice Exposed to Sodium Arsenite through Drinking Water

Objective To explore the effects of exogenous methionine on arsenical distribution in liver,blood and brain of mice exposed to sodium arsenite through drinking water. Methods The female Kunming mice were randomly divided into control group, the alone arsenic exposure group , the low level methionine intervention group, the moderate level methionine intervention group and the high level methionine intervention group, eight mice in each group . The mice in the experimental groups were exposed to sodium arsenite through drinking water at 50 mg/L arsenic for four consecutive weeks. And at the fourth week the 5 groups were treated intraperitoneally with saline solution (control and As group), 100 mg/kg b.w,200 mg/kg b.w or 400 mg/kg b.w methionine, respectively . Twenty-four hours after cessation of methionine administration, mice were anaesthetized and rapidly dissected. The samples of blood, liver and brain were removed immediately for arsenic species analysis. Levels of inorganic arsenic (iAs),monomethylarsonic acid (MMA) and dimethylarsenic acid (DMA) were determined by HG-AAS method. Then total arsenic speciation(TAs), primary methylation ratio(PMR)and secondary methylation ratio(SMR)in each tissue were calculated. Results Compared with the control group, the levels of iAs, MMA, DMA and TAs in liver, brain and blood, were significantly higher in all experimental groups (P<0.05). Compared with those in mice exposed to arsenite alone,levels of DMA and PMR in the moderate and high level methionine groups were significantly higher in liver( P<0.05); levels of iAs, MMA and TAs in blood in all methionine intervention groups were much lower (P<0.05); and levels of DMA and TAs in all the methionine intervention groups were significantly decreased in brain (p<0.05). Conclusion Exogenous methionine can regulate arsenic methylation in liver, and promote excretion of methylated arsenic, therefore reduce arsenic levels in both blood and brain.