摘要
为探讨亚砷酸钠(NaAsO_(2))对昆明小鼠的主要脏器指数(肝、肺、脾、膀胱)和尿砷代谢与暴露途径的关系,本研究将昆明小鼠随机分为对照组、灌胃组和气管滴注组,给予不同剂量亚砷酸钠暴露12周。每周监测小鼠体质量,定期收集尿液,并通过原子荧光光谱法测定尿砷浓度,实验终点测定脏器指数。结果显示,亚砷酸钠经2种途径暴露后,暴露组体质量显著低于对照组(P<0.05),体质量变化呈典型的“先升后降”模式,表明2种暴露途径均导致显著的全身毒性反应。脏器指数分析显示,除灌胃组的肺脏指数升高差异无统计学意义外,其余脏器指数均显著升高(P<0.05),其中气管滴注暴露的肺脏指数增幅最大,气管滴注暴露呈现明显的肺脏靶向毒性。2种暴露途径下低剂量组膀胱指数均呈非单调性升高(P<0.05),小鼠膀胱可能通过上皮增生等代偿机制响应砷暴露。尿砷动力学显示,灌胃组表现出比气管滴注组更快的砷排泄速率和更高的尿砷浓度,表明灌胃暴露可能通过增强肝脏代谢转化促进砷的尿排泄。研究表明,暴露途径对亚砷酸钠的毒代动力学特征具有显著的影响,不同途径通过改变吸收效率和首过代谢程度,进而影响全身砷负荷及器官特异性毒性分布。本研究揭示了不同途径砷暴露对小鼠的毒作用机制,强调暴露途径在调节砷吸收、代谢和毒性中的重要作用,为制定基于暴露途径的差异化防控策略提供依据。
This study aimed to investigate the relationship between sodium arsenite(NaAsO_(2))exposure routes and their effects on organ indices(liver,lung,spleen,bladder)and urinary arsenic metabolism in Kunming mice.The mice were randomly allocated to control,gastric lavage,and intratracheal instillation groups,which were exposed to different doses of NaAsO_(2)for 12 weeks.Mouse body weights were monitored weekly.Urine samples were collected periodically,and urinary arsenic concentration was determined by atomic fluorescence spectrometry.O rgan indices were measured at the end of the experiment.The results showed that the exposed groups exhibited significantly decreased body weight compared with the control group(P<0.05),following an increase-then-decrease pattern,indicating systemic toxicity from both exposure routes.Quantitative analysis of organ indices showed significant increases in all organ indices except for lung indices in the gastric lavage groups(P<0.05),indicating possible involvement of multiple organs.Among these,the lung indices showed the most pronounced increase in the intratracheal instillation groups compared with other exposure routes(P<0.05),illustrating route-specific p ulmonary toxicity.Notably,both exposure routes resulted in a significant non-monotonic increase in bladder i ndices(P<0.05),which may reflect compensatory epithelial hyperplasia induced by arsenic exposure.Furthermore,analysis of urinary arsenic metabolites showed that the gastric lavage groups had significantly higher urinary arsenic concentrations and faster urinary excretion rates compared with the intratracheal instillation groups(P<0.05).This results suggest that enhanced hepatic metabolic conversion may facilitate urinary elimination in the gastric lavage groups.The study indicates that exposure routes significantly influence the toxicokinetic characteristics of NaAsO_(2).Different exposure routes modulate arsenic absorption efficiency and first-pass metabolism,thereby affecting s ystemic accumulation patterns and target-organ toxicity.This work systematically demonstrates the toxicological mechanisms of arsenic exposure via different routes in mice,highlighting the importance of exposure route in m odulating arsenic absorption,metabolism,and toxicity.These results provide a scientific basis for developing route-specific prevention and control strategies.
作者
颜正毅
郝雅婷
项发艳
晏闻婷
张潭
张益发
徐丹先
文卫华
YAN Zhengyi;HAO Yating;XIANG Fayan;YAN Wenting;ZHANG Tan;ZHANG Yifa;XU Danxian;WEN Weihua(School of Public Health,Dali University,Dali 671003,China;Yunnan Center for Disease Control and Prevention(Yunnan Academy of Preventive Medicine),Kunming 650034,China)
出处
《生态毒理学报》
北大核心
2025年第6期397-405,共9页
Asian Journal of Ecotoxicology
基金
国家自然科学基金项目(82060591)。
关键词
亚砷酸钠
小鼠
慢性毒性
脏器指数
尿砷
气管滴注
灌胃
sodium arsenite
mice
chronic toxicity
organ index
urinary arsenic
intratracheal instillation
gastric lavage
