| Background and purposeFor the treatment of malignant tumors,the conventional methods are surgery,chemotherapy and radiotherapy,but with the progress of society and the improvement of social medical level,molecular targeted therapy has begun to come to the fore and has been valued and accepted by people.Tumor molecular targeting drugs take advantage of the molecular biological differences between cancer cells and normal cells,such as enzymes,genes and transduction signals,and take related technical interventions to inhibit the proliferation of cancer cells and promote the rapid death of cancer cells.Through the treatment of tumor molecular targeted drugs,the mortality of malignant tumor is significantly reduced,and the overall survival rate is significantly improved,which plays an indispensable role in the treatment of malignant tumor.Epidermal growth factor receptor inhibitor(EGFRIs)is a common tumor molecular targeting drug,which is widely used in a variety of cancers,such as lung cancer,head and neck cancer,nasopharyngeal carcinoma and so on.However,the adverse reactions caused by EGFRIs targeted drugs,such as skin rash,diarrhea,interstitial pneumonia.central nervous system lesions and so on,are becoming more and more obvious.The rash caused by EGFRIs targeted drugs is the most common adverse reaction.As the conclusion that there is a positive correlation between the severity of skin rash caused by EGFRIs targeted drugs and the anti-tumor efficiency has been confirmed,interrupting the treatment of targeted drugs will seriously affect the survival rate of tumor patients,and the consequences are unimaginable,so it is particularly important to seek drugs that can improve the rash caused by EGFRIs targeted drugs.According to the incidence and severity of the rash,the commonly used treatment is mainly local and systemic treatment,through smearing Vaseline or hormone ointment,or taking some antibiotics and antihistamines such as diphenhydramine.However,long-term use of hormone drugs will increase skin sensitivity and tenderness,accompanied by symptoms such as dryness,chapping and pigmentation.Some are even more likely to cause secondary infection,oral antibiotics or antihistamines,the improvement of skin rash is not only very limited,but also produce hepatorenal toxicity,affect the quality of life of patients to a certain extent,and may even aggravate the patient's condition.Therefore,it is particularly important to find drugs that can treat EGFRIs-induced rash without increasing any side effects.In recent years,traditional Chinese medicine has gradually become a new and effective way to treat rash caused by EGFRIs targeted drugs.The traditional prescription of traditional Chinese medicine The treatment principle of "tonifying qi and blood,clearing heat and detoxification" has been proved to have a good clinical effect in the treatment of related rash,with an effective rate as high as 90%.However,the mechanism of the effect of this prescription on related rash is not clear.In order to further study the molecular mechanism of"Qiyinsanliangsan" in the treatment of rash,relevant basic experimental research has been carried out.MethodsThis study is mainly divided into three parts:Experiment 1:Study on the skin barrier function of the animal model of skin rash induced by gefitinib in the traditional Chinese medicine prescription " Qiyinsanliangsan".The differentiation of keratinocytes and the expression of aquaporin in epidermis before and after treatment with traditional Chinese medicine prescription were compared by means of Western blot and immunohistochemistry.Experiment 2:The study of the traditional Chinese medicine prescription "Qiyinsanliangsan" on the skin inflammatory response of the animal model of skin rash induced by gefitinib.Whether the traditional Chinese medicine prescription interfered with the polarization of macrophages in animal epidermis and its effects on mast cells,natural killer cells and pro-inflammatory factor TREM-1 by means of immunohistochemistry.Experiment 3:The effect of traditional Chinese medicine prescription"Qiyinsanliangsan" on the quantity of antimicrobial peptides in animal model of skin rash induced by gefitinib.RT-PCR technique and immunohistochemical technique were used to compare the quantitative changes of antimicrobial peptide CAMP at mRNA level and protein level before and after treatment with traditional Chinese medicine prescription.ResultsExperiment 1:By comparing the positive expression of specific protein and aquaporin in keratinocyte differentiation before and after treatment with traditional Chinese medicine,and making a quantitative analysis,the experimental results show that the traditional Chinese medicine prescription "Qiyinsanliangsan" can increase the differentiation of keratinocytes,reduce the thinning of cuticular layer caused by excessive apoptosis,increase the content of aquaporin,reduce itching caused by skin dryness and restore skin elasticity.Experiment 2:By comparing the secretion of relevant immune cells and pro-inflammatory factors before and after the treatment of traditional Chinese medicine,the experimental results show that the traditional Chinese medicine prescription"Qiyinsanliangsan" can induce the transformation of pro-inflammatory M1 macrophages into anti-inflammatory M2 macrophages,reduce the infiltration of related macrophages,mast cells,natural killer cells and TREM-1,and repair the inflammatory state in the skin.The reason for relieving itching is closely related to the decrease in the number of mast cells.Experiment 3:By comparing the expression of antimicrobial peptides in mRNA and protein levels in the skin before and after treatment with traditional Chinese medicine,the experimental results show that the traditional Chinese medicine prescription"Qiyinsanliangsan" can reduce the overexpression of antimicrobial peptides at the mRNA and protein levels,alleviate the excessive defense caused by the overexpression of antimicrobial peptides,and draw the conclusion that the best dose of the experimental prescription to down-regulate the content of antimicrobial peptides is the middle dose of the experimental prescription.It laid the dose foundation for the following experimental research.ConclusionThe traditional Chinese medicine prescription "Qiyinsanliangsan" takes "tonifying qi and blood,clearing heat and detoxification" as the new treatment principle,which can improve the skin barrier function of skin rash model rats.it has a good effect in repairing inflammatory injury and relieving excessive defense of antimicrobial peptides. |
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