朱砂在大鼠体内的汞形态分析及连续给药后的组织分布研究  

Mercury species analysis and tissue distribution in rats after continuous administration of Cinnabaris

作　　者：何春娇 骆骄阳[2] 阮豪南 罗雅雯 柯童炜 秦旭华[1] 杨美华[2] HE Chun-jiao;LUO Jiao-yang;RUAN Hao-nan;LUO Ya-wen;KE Tong-wei;QIN Xu-hua;YANG Mei-hua(Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China;Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine,Ministry of Education,Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100193,China)

机构地区：[1]成都中医药大学,四川成都611137 [2]中国医学科学院,北京协和医学院,药用植物研究所,中草药物质基础与资源利用教育部重点实验室,北京100193

出　　处：《中国中药杂志》2023年第22期6173-6182,共10页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(82074009);中国医学科学院医学与健康科技创新工程协和重大协同创新项目(2021-I2M-1-031);国家外国专家人才类项目(G20200001511)。

摘　　要：朱砂是临床上常用的镇静、安神中药,其安全性一直备受关注。该文拟研究连续给予朱砂后,大鼠体内的汞形态及组织分布。将30只大鼠随机分为对照组(等量0.5%羧甲基纤维素钠)、朱砂低剂量组(0.2 g·kg^(-1))、朱砂高剂量组(2 g·kg^(-1))、伪无菌对照组(等量0.5%羧甲基纤维素钠)、伪无菌朱砂组(2 g·kg^(-1)),连续灌胃给药30 d。通过建立超声辅助-酸提取法与高效液相色谱-电感耦合等离子体质谱(high performance liquid chromatography and inductively coupled plasma-mass spectrometry,HPLC-ICP-MS)联用技术对大鼠不同组织、血浆、尿液和粪便中无机汞[inorganic mercury,Hg(Ⅱ)]、甲基汞(methylmercury,MeHg)和乙基汞(ethylmercury,EtHg)进行测定。优化确定了最佳检测条件和提取方法,各汞形态的线性(R~2>0.999 3)、精密度(RSD<7.0%)及准确度(加样回收率为73.05%~109.5%)良好,满足分析要求。汞形态检测结果显示Hg(Ⅱ)在5个实验组的组织中均有检出,主要蓄积脏器为肠道、胃和肾脏;MeHg在大部分组织中以较低的浓度存在;所有组别组织中EtHg均未检出。此外,病理学结果表明,朱砂高、低剂量组和伪无菌朱砂组中可见肝细胞空泡变性,细胞胞浆疏松、淡染,单核性细胞浸润,朱砂低剂量组病变程度略轻。朱砂高剂量组和伪无菌朱砂组可见肾脏肾小管上皮水样变性,其余各组与对照组比较没有明显差异。各组大鼠脑组织未见异常改变。该文研究了朱砂连续给药30 d在正常和伪无菌大鼠体内不同汞形态和组织分布,并阐明了其对肝脏、肾脏和脑组织的影响,为朱砂的安全性评价提供了数据支撑。Cinnabaris is a traditional Chinese medicine(TCM) commonly used for sedation and tranquilization in clinics,and its safety has always been a concern.This study intends to investigate the species and tissue distribution of mercury in rats after continuous administration of Cinnabaris.In the experiment,30 rats were randomly divided into the control group(equivalent to 0.5% carboxy-methyl cellulose sodium),low-dose Cinnabaris group(0.2 g·kg^(-1)),high-dose Cinnabaris group(2 g·kg^(-1)),pseudogerm-free control group(equivalent to 0.5% sodium carboxymethyl cellulose),and pseudogerm-free Cinnabaris group(2 g·kg^(-1)).They were orally administered for 30 consecutive days.Ultrasound-assisted acid extraction method combined with high performance liquid chromatography and inductively coupled plasma-mass spectrometry(HPLC-ICP-MS) was adopted to determine inorganic mercury [Hg(Ⅱ)],methylmercury(MeHg),and ethylmercury(EtHg) in different tissue,plasma,urine,and feces of rats.The optimal detection conditions and extraction methods were optimized,and the linearity(R~2>0.999 3),precision(RSD<7.0%),and accuracy(spike recoveries ranged from 73.05% to 109.5%) of all the mercury species were satisfied,meeting the requirements of analysis.The results of mercury species detection showed that Hg(Ⅱ) was detected in all the tissue of the five experimental groups,and the main accumulating organs were the intestinal tract,stomach,and kidney.MeHg existed at a low concentration in most tissue,and EtHg was not detected in all groups.In addition,pathological examination results showed that hepatocyte vacuolar degeneration,loose cytoplasm,light staining,and mononuclear cell infiltration were observed in the high-dose Cinnabaris group,low-dose Cinnabaris group,and pseudogerm-free Cinnabaris group,with slightly milder lesions in the low-dose Cinnabaris group.Hydrous degeneration of renal tubular epithelium could be seen in the high-dose Cinnabaris group and pseudogerm-free Cinnabaris group,but there was no significant difference between the

关 键 词：朱砂 大鼠 汞形态 组织分布 病理 

分 类 号：R285.5[医药卫生—中药学]