摘要
研究矿物药朱砂中汞(Hg)及微量金属元素对小鼠肝脏的毒性作用,并对比朱砂与Hg、硒(Se)的毒性大小,从而为朱砂的安全用药提供建议。将雄性KM小鼠分为空白组,朱砂低、高剂量组(50、200 mg·kg^(-1)),朱砂安神丸(ZSASW)组(600 mg·kg^(-1)),HgS组(50 mg·kg^(-1)),Hg(NO_(3))_(2)组(1.2 mg·kg^(-1)),Na_(2)SeO_(3)组(1 mg·kg^(-1)),HgS-Na_(2)SeO_(3)组(HgS 50 mg·kg^(-1),Na_(2)SeO_(3)1 mg·kg^(-1)),ZS-Na_(2)SeO_(3)组(ZS 50 mg·kg^(-1),Na_(2)SeO_(3)1 mg·kg^(-1)),ZSASW-Na_(2)SeO_(3)组(ZSASW 600 mg·kg^(-1),Na_(2)SeO_(3)1 mg·kg^(-1)),每组8只,连续灌胃1个月。苏木精-伊红(HE)染色观察小鼠肝脏组织病变;DNA断裂的原位末端标记法(TUNEL)法分析小鼠肝脏细胞的凋亡情况;全自动生化仪检测小鼠血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、谷氨酰基转移酶(γ-GT)的含量;电感耦合等离子体质谱(ICP-MS)法测定小鼠肝脏中的微量金属元素含量;冷原子吸收测汞仪及原子荧光分光光度计分别测定小鼠肝脏中的Hg、Se含量。结果表明朱砂高剂量组、Na_(2)SeO_(3)组、Hg(NO_(3))_(2)组小鼠肝脏细胞有不同程度的肿胀、细胞边界模糊或皱缩现象;TUNEL实验结果表明朱砂高剂量组、Na_(2)SeO_(3)组、Hg(NO_(3))_(2)组小鼠部分肝脏细胞有变大的趋势;朱砂低剂量组小鼠的ALT含量明显低于空白组,Na_(2)SeO_(3)组小鼠肝脏的γ-GT含量也明显低于空白组,而HgS-Na_(2)SeO_(3)组和Hg(NO_(3))_(2)组小鼠血清γ-GT明显高于空白组,Na_(2)SeO_(3)组小鼠肝脏的AST含量也明显高于空白组;各给药组小鼠肝脏中的微量元素含量与空白组比较无显著差异,小鼠肝脏中含量较高的微量金属元素为镁(Mg)、钙(Ca)、铁(Fe),含量较低的为钪(Sc)、钛(Ti)、钒(V)、铬(Cr)、锰(Mn)、钴(Co)、镍(Ni)、锶(Sr);各个给药组与空白组小鼠肝脏Hg含量RSD为136%,含Hg最高的为朱砂高剂量组(16.66μg·g^(-1)),最低的为HgS-Na_(2)SeO_(3)组(0.5μg·g^(-1));各个给药组与空白组小鼠肝脏Se含量RSD为11%,含Se最高的为ZSASW-Na_(2)SeO_(3)组(4.95μg·g^(-1)),最低的为ZSASW组(3.50μg·g^(-1))。实验结果表明,朱砂及其复方ZSASW的毒性远小于Hg(NO_(3))_(2)、Na_(2)SeO_(3)。肝脏中Hg含量与给药剂量成正相关,且Se对Hg有一定的拮抗作用。朱砂在有医师指导下按照正确的服药剂量、服药时间科学使用时是安全无毒的。
The toxic effects of mercury and trace metal elements in cinnabar on the liver of mice were investigated,and the toxicity of cinnabar was compared with that of mercury(Hg)and selenium(Se),in order to provide suggestions for the safe use of cinnabar.Male KM mice were divided into control group,low-dose(50 mg·kg^(-1))and high-dose(200 mg·kg^(-1))cinnabar groups,cinnabar tranquilizing pill(ZSASW)group(600 mg·kg^(-1)),HgS group(50 mg·kg^(-1)),Hg(NO_(3))_(2)group(1.2 mg·kg^(-1)),Na_(2)SeO_(3)group(1 mg·kg^(-1)),HgS-Na_(2)SeO_(3)group(HgS:50 mg·kg^(-1),Na_(2)SeO_(3):1 mg·kg^(-1)),ZS-Na_(2)SeO_(3)group(ZS:50 mg·kg^(-1),Na_(2)SeO_(3):1 mg·kg^(-1)),and ZSASW-Na_(2)SeO_(3)group(ZSASW:600 mg·kg^(-1),Na_(2)SeO_(3):1 mg·kg^(-1)),with eight mice in each group.They were administered intragastrically for one month continuously.Hematoxylin-eosin(HE)staining was used to observe the pathological changes in the liver tissue of mice.The apoptosis of liver cells in mice was analyzed by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)method.The content of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and gamma-glutamyl transferase(γ-GT)in the serum of mice was detected by an automatic biochemical analyzer.The content of trace metal elements in the liver of mice was determined by inductively coupled plasma mass spectrometry(ICP-MS).The content of Hg and Se in the liver of mice was determined by a cold atomic absorption spectrometer and an atomic fluorescence spectrometer,respectively.The results showed that the liver cells of mice in the high-dose cinnabar group,the Na_(2)SeO_(3)group,and the Hg(NO_(3))_(2)group had different degrees of swelling and blurred or shrunken cell boundaries.The TUNEL experiment results showed that some liver cells in the high-dose cinnabar group,the Na_(2)SeO_(3)group,and the Hg(NO_(3))_(2)group had a tendency to be larger than other cells.The ALT content in the low-dose cinnabar group was significantly lower than that in the control group,and theγ-GT content in the liver of mice in the Na_(2)SeO_(3)group was also significantly lower than that in the control group.However,theγ-GT level in the serum of mice in the HgS-Na_(2)SeO_(3)group and the Hg(NO_(3))_(2)group was significantly higher than that in the control group,and the AST content in the liver of mice in the Na_(2)SeO_(3)group was also significantly higher than that in the control group.There was no significant difference in the content of trace metal elements in the liver of mice in each drug administration group compared with that in the control group.The trace metal elements with the highest content in the liver of mice were magnesium(Mg),calcium(Ca),and iron(Fe).The elements with the lowest content were scandium(Sc),titanium(Ti),vanadium(V),chromium(Cr),manganese(Mn),cobalt(Co),nickel(Ni),and strontium(Sr).The relative standard deviation(RSD)of Hg content in the liver of mice in each drug administration group compared with that in the control group was 136%.The highest Hg content was found in the mice in the high-dose cinnabar group,which was 16.66μg·g^(-1),and the lowest Hg content was found in the liver of mice in the HgS-Na_(2)SeO_(3)group,which was 0.5μg·g^(-1).The RSD value of Se element content in the liver of mice in each administration group compared with that in the control group was 10.63%.The lowest Se content was in the ZSASW group,which was 3.50μg·g^(-1),and the highest was in the ZSASW-Na_(2)SeO_(3)group,which was 4.95μg·g^(-1).The above experiments indicated that the toxicity of cinnabar and its compound ZSASW was much lower than that of Hg(NO_(3))_(2)and Na_(2)SeO_(3).The content of Hg element in the liver was positively correlated with the administration dose,and Se element had a certain antagonistic effect on Hg element.When cinnabar was used scientifically under the guidance of a physician with the correct dosage and administration time,it was safe and non-toxic.
作者
卓鱼周
戴智慧
韩子颜
张欣慧
刘昱言
朱冰倩
陈丽君
吴佳宜
柴卓毓
ZHUO Yu-zhou;DAI Zhi-hui;HAN Zi-yan;ZHANG Xin-hui;LIU Yu-yan;ZHU Bing-qian;CHEN Li-jun;WU Jia-yi;CHAI Zhuo-yu(Mineral Medicine Research Center,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;State Key Laboratory of Critical Mineral Research and Exploration,Institute of Geochemistry,Chinese Academy of Sciences,Guiyang 550081,China)
出处
《中国中药杂志》
北大核心
2025年第22期6363-6371,共9页
China Journal of Chinese Materia Medica
基金
贵州省科技计划项目(黔科合基础-ZK[2024]一般348,黔科合基础-ZK[2022]一般514)
国家自然科学基金项目(42273083,42077313)
贵州省大学生创新创业训练计划项目(S2024106621500)
贵州中医药大学大学生创新创业训练计划项目(贵中医大创合字[2024]123号)
贵州省科技计划项目(GZ 2020SIG)。
关键词
细胞凋亡
微量元素
硒-汞拮抗
增效减毒
朱砂
矿物药
cell apoptosis
trace element
selenium-mercury antagonism
efficiency increase and toxicity decrease
cinnabar
mi-neral drug
