The Study Of Realgar's Intestinal Toxicity And Its Mechanism Of Detoxicity By Compatibility Of Salvia Miltiorrhiza

Realgar,also known as shihuang,cockscomb stone and huangjingshi,is a common mineral and heavy metal traditional Chinese medicine.It has been defined as As₂S₂with a little soluble arsenic trioxide?As₂O₃?in Chinese pharmacopoeia Since 1985.Realgar preparations are widely used in clinical practice,including realgar-Indigo naturalis formula,niuhuang antidote pills,liushen pills,and angong niuhuang pills.Acute Promyelocytic Leukemia?APL?is a special type of Acute myeloid Leukemia with an early death rate of more than 90%.It is one of the most difficult leukaemia to cure.Until the 1980s,APL has the potential to be cured after a bold attempt at arsenic.Arsenic preparation has good effectiveness,but the adverse reactions are obvious,including cardiac toxicity,liver toxicity,gastrointestinal toxicity and so on.In recent years,the medical found realgar can be used to treat malignant diseases,such as blood and tumor.Compound huangdai tablet is a compound created by professor Huang shilin according to the idea of emperor?realgar?,minister?indigo naturalis?,salvia?salvia miltiorrhiza?and prince?radix pseudostellariae?.It has been clinically proved that the remission rate of APL treatment is higher than 90%,which is equivalent to the first-line drug As2O3.And it has the characteristics of less adverse reactions and lower recurrence rate compared with As2O3,which has great medicinal and research value.The adverse reactions of realgar mainly include intestinal toxicity,cardiac toxicity and liver toxicity.According to literature review,there are some studies have been focused on cardiac toxicity and liver toxicity,but only a few studies on intestinal toxicity.Intestinal toxicity can cause drug absorption disorders,inaccurate dosage,poor quality of life,and even life-threatening in patients with severe diarrhea.As one of the response criteria of intestinal toxicity,the degree of disorder of intestinal flora is positively correlated with intestinal toxicity.Therefore,this study took intestinal flora as the entry point to observe the intestinal toxicity of realgar and tried to improve the intestinal toxicity with salvia miltiorrhiza.Starting from intestinal flora,this study preliminarily studied the intestinal toxicity of realgar and its possible improvement mechanism.In order to provide a new eye for the study of intestinal toxicity of realgar and its compounds.First,the effects of realgar on gastrointestinal kinetic energy and intestinal flora and intestinal structure were studied by gavage treatment of normal mice.And the mechanism of intestinal toxicity of realgar was elucidated.Secondly,building the intestinal flora disturbance model,To study the effects of disordered intestinal flora on the toxicity and mechanism of realgar.Finally,the construction of APL mice model,To study the effect of salvia miltiorrhiza on the gastrointestinal toxicity of realgar and its possible mechanism.The results show that:?1?Realgar could increase the gastric residual rate and decrese the rate of intestinal progression in Babl/C mice.Realgar could affect the intestinal flora,which showing decreased firmicutes and bacteroidetes and increased proteobacteria,which were related to the dose.The high dose group of realgar could cause jejunum ileum inflammatory edema.?2?Compared with wild type C57 mice,the toxicity of realgar in intestinal flora disturbance mice model is incresed.Realgar can reduce the expression of tight junction proteinsintestinal ZO-1 and MUC2 in the jejunum,ileum,mucins.It can also improve the r intestinal permeability in intestinal flora disorde mice,and increase intestinal flora disturbance.Fecal microbiota transplantation can repair the intestinal mucosal barrier to alleviate the toxic effects of realgar,and improve survival dose group mice intestinal flora disturbance model.?3?Realgar disrupts the intestinal flora of APL mice,and reduces the expression of tight junction protein ZO-1 in jejunum ileum,also decreases the expression of MUC2 mucin,and improves the intestinal permeability of APL mice.Salvia miltiorrhiza can repair the intestinal mucosal barrier,reduce the intestinal permeability of APL mice,and alleviate the toxic effect of realgar.