铅暴露对大鼠孕期骨铅动员及骨微结构的影响

Effects of lead exposure on bone lead mobilization and bone microstructure in pregnant rats

目的探讨孕前铅暴露对大鼠孕期骨铅动员及骨微结构的影响,为孕期骨铅动员的潜在机制研究提供依据。方法26只SPF级刚断乳雌性Wistar大鼠,随机分入暴露组和对照组,采用自由饮水方式分别给予0.05%醋酸铅溶液和醋酸钠溶液,4周后改饮蒸馏水,铅暴露洗脱4周后,与同周龄健康雄鼠合笼受孕;分别在孕期第3、10、17天(GD3、GD10、GD17)收集雌鼠全血、股骨和胫骨标本,采用电感等离子体质谱法测定血铅和骨铅;采用微计算机断层扫描仪扫描GD17单侧股骨,观察密质骨和松质骨微结构改变情况;股骨采用苏木精-伊红染色,观察骨结构和形态变化。结果实验期间两组大鼠精神、活动和被毛光泽度良好,体重稳定增长且无明显差异。暴露组大鼠GD17时血铅水平,GD3、GD10、GD17时骨铅水平均高于对照组(P<0.05);GD17时暴露组大鼠松质骨铅水平明显低于GD10时(P=0.015)。松质骨铅与血铅之间呈负相关(r=-0.578,P=0.049),骨铅对血铅的贡献率为26.8%。骨组织形态分析显示暴露组雌鼠GD17时松质骨的骨量减少,骨小梁数目、厚度及紧密程度均下降,骨小梁间隙增大,骨小梁面积比例较对照组减少了27.34%(t=2.851,P=0.046)。结论大鼠孕前铅暴露促进松质骨铅释放入血,并影响骨微结构,孕晚期存在骨铅动员现象。

Objective To investigate the effect of lead exposure before pregnancy on bone lead mobilization and bone microstructure in pregnant rats,so as to provide the evidence for illustrating the potential mechanisms of bone lead mobilization during pregnancy.Methods Twenty-six weaning female specific pathogen-free(SPF)rats of the Wistar strain were randomly divided into the exposure group and the control group.Rats in the exposure group were given 0.05%lead acetate solution for weeks,while animals in the control group were given 0.05%sodium acetate solution.Then,rats in both groups were given distilled water.Following removal of lead exposure for 4 weeks,female rats were co-caged with healthy males at the same age until pregnancy.The blood,femur and tibia specimens were collected from female rats on days 3(GD3),10(GD10)and 17(GD17)at pregnancy,and the blood and bone lead levels were measured using inductively coupled plasma mass spectrometry(ICP-MS).The unilateral rat femur was scanned using micro-computed tomography(micro CT),and the microstructure changes of cortical and trabecular bones were investigated.The structural and morphological changes of rat femur were observed using hematoxylin-eosin(HE)staining.Results During the study period,satisfactory mental status and activity and good coat glossiness were observed in female rats in both groups,and there was no significant difference in the increase of rat body weight between groups.The blood lead level at GD17 and bone lead levels at GD3,GD10 and GD17 were significantly higher in rats in the exposure group than in the control group(P<0.05),and the trabecular bone lead level was significantly lower in rats in the exposure group at GD17 than at GD10(P=0.015).The trabecular bone lead level correlated negatively with blood lead level(r=-0.578,P=0.049),and bone lead contributed 26.8%to blood lead.The bone mass,trabecular number,thickness and density of female rat trabecular bones all reduced in the exposure group at GD17,with an increase in trabecular space,and the proportion of trabecular areas reduced by 27.34%in the exposure group relative to the control group(t=2.851,P=0.046).Conclusions Lead exposure before pregnancy promotes the release of lead from trabecular bones into blood and affects bone microstructure in rats.There is bone lead mobilization during late pregnancy.