| Objective:Realgar is a traditional Chinese medicine containing arsenic and has a wide range of clinical applications.It is one of the 28 toxic Chinese medicines specified by the State Council in the Measures for the Administration of Toxic Drugs for Medical Drugs.Due to the influence of traditional medication habits(no toxic side effects of traditional Chinese medicine),there have been reports of drug-induced arsenic poisoning caused by unreasonable(long-term,excessive and non-standard)rational use of single-flavored realgar or its compound preparations,many of which have been reported.It is caused by the abuse of newborns and children.Its clinical manifestations are systemic multi-system damage,mainly caused by nervous system,digestive system and skin damage.Modern studies have shown that arsenic can accumulate in the brain tissue through the blood-brain barrier,causing spatial learning and memory and obstacle recognition in new animals.Epidemiological investigations have shown that long-term arsenic exposure can lead to language,cognitive,behavioral,hearing and motor impairments.Therefore,the exposure and accumulation effects of arsenic caused by realgar have made the safety of royal jelly-containing medicines controversial,especially in children's medication,which has seriously affected the international reputation of realgar containing Chinese medicine.Studies have shown that the mechanism of rhubarb/arsenic-induced neurotoxicity is mainly oxidative stress and oxidative damage,while arsenic is a strong inducer of Nrf2,a class of crucial receptors in learning and memory processes,but related The role of Nrf2/ARE signal transduction pathway and NMDA receptor in oxidative damage induced by realgar has not been fully elucidated and needs further study.In addition,Calculus Bovis(CB)is a natural antioxidant that antagonizes a variety of toxic-induced oxidative stress injuries.In proprietary Chinese medicines,bezoar is often compatible with realgar,which has a combined detoxification effect.In summary,this study will establish all the information databases containing realgar Chinese patent medicines contained in the current four national standards in China,with the main line of children's medicines,comprehensively and systematically on the shape,prescription,usage and dosage of Chinese patentmedicines,and matters needing attention.Detailed classification and statistics,summarizing the problems found and making reasonable suggestions to provide reference for the safe and rational use of pediatric drugs containing realgar Chinese patent medicine.In addition,the primary neuron cell model of realgar exposed rats was established by in vitro experiments,and the protective effect of the yellow-induced neurocytotoxicity was observed by using bezoar,from the perspective of Nrf2/ARE signal transduction pathway and NMDA receptor.The mechanism is discussed to provide new ideas for the prevention and treatment of realgar or chronic arsenic poisoning and the mechanism of detoxification of bezoar and realgar.Methods: All the realgar-containing Chinese patent medicines contained in the current four national standards are used as research objects.The database is established based on the name,traits,prescription,function and indications,usage and dosage,and precautions.In the function and treatment,adults and Children,children,etc.are used as keywords to establish an analysis database in the field.The SPSS19.0statistical software was used to describe and analyze the composition ratio or percentage method of the respondents.Based on this database,detailed classification and statistics were carried out on the traits,prescriptions,usage and dosage,and precautions.In vitro experiments were performed within 24 hours after birth of newborn SD rats.Brain extraction,isolation,purification and identification were performed.After calculating the positive cell rate of more than 80%,the time and dose of realgar exposure and artificial bezoar pre-intervention were determined by MTT method.Colorimetric method,micro-enzyme labeling method and TBA method were used to determine the content of LDH,GSH and MDA,and the protein expression levels of Nrf2,Keap1,HO-1,NR2 A and NR2 B were determined by Western blot.The data obtained by the experiment were average ± standard.Differences were marked with SPSS19.0 software One Way ANOVA and Two Way ANOVA.The significance of the differences between groups was statistically significant.P<0.05 was considered statistically significant.Results: 1.The statistical results show that there are 187 kinds of realgar medicines containing realgar in the current four national standards,including 50 kinds ofChinese patent medicines(26.74%)and 25 kinds of pediatric Chinese patent medicines(13.37%).(1)There are 5 dosage forms of realgar and pediatric Chinese patent medicines containing realgar,which are ordered by order: pills,tablets,powders,capsules,other preparations,among which the number of big honey pills is the most;(2)There are only 5 kinds of toxic medicinal materials containing realgar in the realgar containing Chinese realgar,29 kinds of toxic medicines,11 kinds of toxic medicines,and 5 kinds of toxic medicines,and 5 kinds of toxic medicines in pediatrics.The proportion of the three toxic substances was the highest(44.00%),followed by the toxic substances containing more than 3 kinds(28.00%);(3)39 of the medicinal products containing realgar in the children were not marked with the dosage of children,and contained the realgar.In the usage and dosage of traditional Chinese medicine,infants,young children,children,etc.,which have unclear age descriptions,account for 68.00%.There are 12 varieties of “conform to doctors”,and there are 32 varieties of “discretionary increase” or “discretion reduction”..Among the children involved in the use of realgar,the unidentified course of treatment was98.00%,and the pediatric containing androgen Chinese medicine used in the dosage did not indicate the treatment course accounted for 96.00%;(4)There were 35 varieties of children involved in the labeling of realgar-containing Chinese medicine.There are 15 varieties with no precautions,and 7 varieties with hobbies containing realgar Chinese patent medicines,and 18 unlabeled varieties.2.The experimental results show that(1)with the increase of dose and time of realgar,the neuron activity decreases and the morphology changes,and there is a dose-time-dependent effect.The artificial bezoar reduces the neuron activity induced by realgar.And morphological changes have antagonistic effects.(2)Realgar can significantly reduce the level of GSH in neurons,and the level of MDA increases significantly.Artificial bezoar has an antagonistic effect on the decrease of GSH level and the increase of MDA level induced by realgar.(3)Realgar can significantly increase the expression of Nrf2,Keap1 and HO-1 proteins,artificial bezoar can antagonize the increase of Nrf2,Keap1 and HO-1 protein expression induced by realgar;and realgar can significantly express NR2 B protein.Reduced,artificial bezoar has an antagonistic effect on the reduction of NR2 A protein level induced by realgar;artificial bezoar and realgar have no significant effect on NR2 A protein expression.Conclusion: 1.The dosage form containing realgar Chinese medicine for children and related drugs is unreasonable,the number of toxic medicines is large,the course of treatment and age are not clear,and the warnings of the instructions are not perfect.2.realgar can cause oxidative damage of neurons,and artificial bezoar has antagonistic effect on oxidative damage caused by realgar.Nrf2,HO-1,Keap1 and NR2 B are sensitive targets for the action of androgen and artificial bezoar. |
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