朱砂体内汞暴露与幼鼠记忆功能障碍的相关性
Correlation between in-vivo mercury exposure from Cinnabaris and memory disorders in juvenile rat
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摘要: 朱砂(α-HgS)是传统矿物类中药材，作为重镇安神药，常配伍用于治疗小儿高热惊风。但因其含有大量汞元素，对正处于发育期儿童的中枢神经系统有潜在危害，极可能造成严重的记忆功能障碍。本研究以幼年大鼠为对象，分别灌胃给予低、中、高剂量朱砂，每日1次，连续14周；采用原子荧光光谱法监测不同发育阶段大鼠血汞暴露量；利用HE染色和Morris水迷宫实验考察与记忆相关的组织结构病变与功能改变；通过相关性分析揭示朱砂和记忆功能障碍之间的剂量-血汞暴露量-毒性效应关系。结果显示，大鼠血汞暴露量呈时间和剂量依赖式增高；灌胃14周后，高剂量组大鼠海马锥体细胞出现核固缩、排列紊乱等病理改变；与对照组相比，高剂量组大鼠在水迷宫实验中的平台与目标象限潜伏期显著延长，目标象限停留时间显著缩短；且朱砂剂量与血汞暴露量间、血汞暴露量与记忆功能障碍间均存在显著的相关性。因此，幼年大鼠长期超量摄入朱砂，会增高体内汞暴露水平，破坏海马组织正常形态结构，导致记忆障碍。本研究为含朱砂儿童专用制剂临床使用的潜在汞中毒风险预警提供了参考。Abstract: Cinnabaris(α-HgS) is a mineral traditional Chinese material medica, as a tranquilizer and sedative, which is widely used in combination with herbs for the treatment of children high fever and convulsion.However, a large amount of mercury in Cinnabaris poses a potential risk to the immature central nervous system of children and probably causes severe memory disorders.Inthisstudy,three groups of juvenile rats were given low, medium, and high doses of Cinnabaris by oral gavage once a day for 14 continuous weeks, respectively.The blood mercury concentrations of the rats at different growth phases were monitored by atomic fluorescence spectrometry.The brain structural and functional changes related to the memory functions were investigated through HE staining and Morris water-maze test. Correlation analysis was conducted to clarify the dose- mercury exposure-toxic effect relationship of Cinnabaris and memory disorders.It was found thatthe blood mercury levels increased in both time- and dose-dependent manner.After the 14-week continuous administration of Cinnabaris, the pathological lesions in hippocampal neurons of rats in the high dose group were observed including pyknosis and disordered cell arrangement.In the Morris water-maze test, compared with the control group, rats in the high dose group exhibited the significantly prolonged latency to find the platform and the target quadrant, and the time spent in the target quadrant was obviously shortened. Thus, the significant correlations were established between Cinnabaris dose and mercury exposure,mercury exposure and memory disorders, respectively. In conclusion, the long-term and overdose administration of Cinnabaris in juvenile rats can increase the in-vivo mercury level, destroy the normal hippocampal morphological structure, and lead to memory disorders. This study provided scientific references for the potential mercury poisoning risks pharmacovigilance of Cinnabaris-containing paediatric formulations.
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Keywords:
- Cinnabaris /
- mercury /
- juvenile rat /
- memory disorders /
- atomic fluorescence spectrometry /
- Morris water-maze test
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