中国公共卫生  2009, Vol. 25 Issue (5): 569-570   PDF    
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于飞, 李岩溪, 任亚浩, 赵越, 智绪平, 杨军, 金亚平. 营养素及DMSA对孕前铅暴露致仔代发育影响[J]. 中国公共卫生, 2009, 25(5): 569-570.
YU Fei, LI Yan-xi, REN Ya-hao, et al. Effects of combined use of DMSA with calcium and ascorbic acid on fetal development in lead intoxicated pregnant mice[J]. Chinese Journal of Public Health, 2009, 25(5): 569-570.
营养素及DMSA对孕前铅暴露致仔代发育影响
于飞1, 李岩溪2, 任亚浩1, 赵越1, 智绪平1, 杨军1, 金亚平3     
1. 中国医科大学公共卫生学院营养与食品卫生教研室, 沈阳 110001;
2. 中国医科大学临床七年制;
3. 中国医科大学公共卫生学院劳动卫生教研室
收稿日期: 2008-09-17
基金项目: 辽宁省自然科学基金(20032063)
作者简介: 于飞(1980-), 男, 辽宁大连人, 讲师, 硕士, 研究方向:营养学。
通讯作者: 金亚平
摘要: 目的 探讨二巯基丁二酸(2, 3-dimercaptosuccinic acid, DMSA)与营养素联合治疗铅中毒孕鼠的效果及对仔鼠生理发育的影响。 方法 空白对照组给予蒸镏水实验组雌鼠经饮水染铅(0.1%的醋酸铅)4周后, 随机分为单纯染铅组、DMSA组、DMSA与钙、维生素C联合组(联合组)。各组小鼠按雌雄比为2:1合笼, 治疗从妊娠第4 d开始, 隔日1次, 至分娩后停止。检测母鼠铅、仔鼠脏器铅、血红蛋白, 并观察仔鼠生理发育状况。 结果 DMSA组与联合组母鼠在治疗后血铅明显低于单纯染铅组, 差异有统计学意义(P < 0.05);DMSA组仔鼠血红蛋白最低, 与空白对照组比较差异有统计学意义(P < 0.05)。DMSA组仔鼠肝铅、骨铅含量最高, 与单纯染铅组、联合组比较, 差异有统计学意义(P < 0.05)。DMSA组仔鼠耳廓分离、出牙达标日龄迟于单纯染铅组, 差异有统计学意义(P < 0.05);联合组仔鼠出牙达标日龄迟于单纯染铅组, 差异有统计学意义(P < 0.05)。 结论 采用DMSA治疗铅中毒孕鼠, 能增加铅通过胎盘进入仔鼠体内, 可导致仔鼠早期生理发育的延缓。
关键词： 铅     二巯基丁二酸     钙     维生素C     孕鼠     仔代    
Effects of combined use of DMSA with calcium and ascorbic acid on fetal development in lead intoxicated pregnant mice
YU Fei, LI Yan-xi, REN Ya-hao, et al     
Department of Public Health, China Medical University, Shenyang 110001, China
Abstract: Objective To study the joint effects of DMSA and nutrients on lead into xicated pregnantmice and the development of their offspring. Methods Fele healthy mice were exposed to 0.1% lead acetate in drinking water for 4 weeks, and then randomly divided in to lead control group, DNSA group and therapeutic alliance group (DMSA+Ca+Vit C).All the felale mice were mated to male by the proportion of 2:1.After the female mice had a pregnancy for four days, the treatment were supplied by gastro gavage every other day during the pregnancy.At the end of the experiment, the blood lead levels of female mice were measured.One to three mouse offspring were taken to measure the Hb content and the lead level in the liver and bone.And then, physio logical developments of the offspring mice were observed and calculated. Results The blood lead levels of female mice in DMDA group and therapeutic alliance group were lower than that of lead control group (P < 0.05).The Hb level of the offspring in DMSA group was the lowest and significantly lower than that of blank control group (P < 0.05).The lead levels in the liver and bone of the offspring in DMSA group were higher than that of lead control group and the rapeutic alliance group (P < 0.05).The time of pinna detachment, tooth growth development of the offspring in DMSA group were later than those of lead control group (P < 0.05).The time of tooth growth of the offspring in therapeutic alliance group was later than those of lead control group (P < 0.05). Conclusion The physiological development of the offspring of the female mice treated with DMSA after lead exposure were delayed because DMSA increased the lead transmitted to the offspring through placenta.
Key words: lead     dimercap to succinic acid     calcium     ascorbic acid     pregnantmice     offspring    

孕期铅中毒的防治不仅可以减少铅对母体健康的损伤，而且可以减少胎儿期的铅暴露，对保证其正常生长发育、减少智力损伤具有重要意义。本研究的前期实验表明，二巯基丁二酸(2，3-dimercaptosuccinic acid, DMSA)联合钙、维生素C同时应用，可大大提高驱铅效果，而且可以降低DMSA的剂量〔1〕。为了解三者联合应用对铅中毒孕鼠的驱铅效果及对仔代生理发育影响。为预防铅对胎儿的生理损害提供基础数据，为孕期铅中毒的综合防治提供科学依据进行了本研究。结果报告如下。

1 材料与方法 1.1 动物分组与处理

选择体重16~18 g的健康昆明种小鼠，雌雄比例为2：1，小鼠适应性饲养1周后，将雌鼠按体重随机分为空白对照组(20只)和染铅组(60只)，空白对照组给予蒸馏水，染铅组给予0.1%的醋酸铅。染铅4周后，对照组不变，将染铅组雌鼠按体重再随机分为：单纯染铅组，DMSA组，DMSA与钙、维生素C联合组(联合组)。然后各组小鼠按雌雄比为2：1合笼，连续10 d。其间每日晨检查阴栓，阳性者记为交配成功。合笼第4 d开始对各组雌鼠进行干预：DMSA组[50 mg/(kg·bw)]和联合组[DMSA50 mg/(kg·bw)]、钙400 mg (kg·bw)(以碳酸钙计)、维生素C 100 mg (kg·bw)]。将DMSA和营养素用蒸馏水制成混悬液，按0.1 mg/10(g·bw)通过灌胃的方式给予，隔日1次，持续至分娩。空白对照组与单纯染铅组则给予同等量的蒸馏水。仔鼠出生后，每窝取1~3只仔鼠取血，分离胸腔骨及肝脏，然后观察并统计各窝仔鼠的生理发育指标。

1.2 检测指标及方法

采用原子吸收分光光度法测定血和脏器铅水平。采用氰化高铁血红蛋白法测定血红蛋白。仔鼠存活率、仔鼠生长发育指标(出生后第1，4，7，21 d称取体重; 分别于出生后第3，7，12 d开始观察耳廓分离、出牙、开眼情况)。

1.3 统计分析

采用SPSS 11.5统计软件进行分析，均数比较用单因素方差分析，率的比较用χ2检验。

2 结果 2.1 雌鼠血铅、仔鼠骨铅水平(表 1)
表 1 各组雌鼠血铅、仔鼠骨铅水平比较(x±s)

表 1结果显示，干预前、后各染铅组血铅水平与对照组比较差异有统计学意义(P < 0.05);干预后的血铅水平，DMSA组和联合组均下降，与单纯染铅组比较，差异有统计学意义(P < 0.05)。仔鼠骨铅含量以DMSA组最高，单纯染铅组、联合组与DMSA组比较，差异有统计学意义(P < 0.05)。

2.2 仔鼠生理指标(表 2)
表 2 各组仔鼠生理指标完成时间(x±s)

表 2结果显示，DMSA组仔鼠耳廓分离、出牙达标日龄均迟于空白对照组和单纯染铅组，差异有统计学意义(P < 0.05);联合组仔鼠出牙达标日龄迟于空白对照组和单纯染铅组，差异有统计学意义(P < 0.05)。

3 讨论

本研究采用孕前铅中毒的模型，是考虑到多数妇女在怀孕期间可能采取了一定措施预防铅暴露，其体内铅含量很可能取决于孕前铅暴露水平〔2〕。研究表明，当环境铅暴露不明显时，骨铅是血铅的主要来源，尤其是怀孕及哺乳期更会动用骨铅的储备〔3〕，母体动员骨铅释出已被证明是胎儿宫内暴露的主要来源〔4〕，DMSA作为一种比较安全特效的络合剂，是目前治疗儿童铅中毒的首选药物〔5〕。动物实验表明，DMSA与营养素联合应用能有效治疗铅中毒〔6〕。结果提示，应用DMSA后，该药本身或其代谢物可能与铅结合生成了一种更容易通过胎盘屏障的复合物，从而导致胎鼠早期生理发育的延缓，这一点也被联合组治疗结果所证明。联合组中补充了钙、维生素C，其仔鼠在血红蛋白及脏器铅水平上与单纯染铅组无明显差异，仅在部分生理发育指标上比空白组有所延迟，可能与钙和维生素C的作用有关。因此，对于孕期铅中毒的药物治疗应慎重考虑。在预防胎儿及婴幼儿铅暴露方面，应主要着眼于一级预防，降低环境中的铅水平，尽量减少孕妇的铅中毒; 或在妊娠前进行驱铅治疗。

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