Study On The Effect And Mechanism Of “Qi Yin San Liang San” On The Adverse Skin Reactions Induced By Gefitini

Research BackgroundAs one of the common cancers,lung cancer can be divided into small cell lung cancer and non-small cell lung cancer(NSCLC)according to histological type.85%of lung cancers belong to NSCLC.In patients with NSCLC,epidermal growth factor receptor(Epidermal Growth Factor Receptor,EGFR)mutations are the most common cause of disease.Epidermal Growth Factor Receptor Inhibitors(EGFRIs)are commonly used drugs for the treatment of NSCLC patients caused by EGFR gene mutations.Compared with chemotherapy drugs,EGFRIs targeted drugs can significantly improve the progression-free survival(PFS)and overall survival(OS)of patients.Nonetheless,when EGFRIs are used clinically,serious adverse reactions will occur and the quality of life of patients will be impaired.Because EGFR is mainly highly expressed in epithelial cells(such as the skin and gastrointestinal tract),the most common adverse reactions of EGFRIs are related to the skin and gastrointestinal tract.Among them,the incidence of rash is the highest.Severe cases will not only affect the quality of life of patients,but also It may also lead to interruption of the treatment process.Therefore,the treatment of related adverse reactions caused by EGFRIs is extremely important to improve the quality of life of patients and treatment compliance.The whole prescription of "Qi Yin Three-liang-Three " granules is simplified in medicine and rigorous in compatibility.The treatment principle is "invigorating qi and blood,clearing away heat and detoxification".The prescription consists of raw astragalus,honeysuckle,angelica,raw licorice,and centipede.Clinical studies have found that " Qi Yin Three-liang-Three " can significantly improve the related skin adverse reactions caused by EGFRIs drugs,with an effective rate of 90%.In order to further clarify the therapeutic mechanism of proven prescriptions,basic experimental research was carried out.In 2009,Surguladze D and others used the EGFR monoclonal antibody ME1 to develop an animal model of EGFR antibody-induced skin rash in SCID mice.However,because SCID mice lack B cells and T cells,these two types of cells are used in SCID mice.The role in animal models has not yet been determined.In 2013,Mascia F and others established a skin rash animal model similar to clinical patients by specifically knocking out EGFR in mouse skin.This animal model can determine whether the rash is a primary disease,but it lacks the process of drugs in the body to treat the disease.The research group used gefitinib to successfully establish an animal model of adverse skin reactions in rats through in vivo administration.However,when the model was modeled at 1.5 times the clinical dose,the weight of the rats decreased significantly and the skin rash was maintained for a short time.In this experiment,the animal model of adverse skin reactions caused by gefitinib was optimized.By adjusting the dosage of the model,the weight loss of the rats during the model was alleviated,and the duration of the rash was maintained.The optimized rat skin adverse reaction animal model was used to intervene,and the effect and mechanism after the intervention were explored.Research Purpose1.Optimize the animal model of adverse skin reactions in BN rats caused by gefitinib2.To explore the effect and mechanism of " Qi Yin Three-liang-Three " in intervention of gefitinib-induced skin adverse reactions in animal models of BN ratsResearch Methods1.Optimize the model of adverse skin reactions in rats caused by gefitinib.By adjusting the dosage and the age of the rat,the weight of the rat and the maintenance time of the rash were observed.2.Use an electronic scale and a biochemical analyzer to observe the effects of "Qi Yin Three-liang-Three" on the weight of the optimized rat model and the biochemical indicators related to liver function in the serum.3.Use skin camera,water loss tester and skin pruritus behavior scoring scale to observe the effect of "Qi Yin Three-liang-Three" on rash,skin moisture loss and skin pruritus in the optimized rat model.4.Use HE staining,immunohistochemistry and Western blot to observe the effect of "Qi Yin Three-liang-Three" on the optimized rat model skin epidermal layer thickness and keratinocyte apoptosis protein.Experimental results1.Optimized animal model of adverse skin reactions in rats,with weight gain and prolonged maintenance time of skin rash.2.Results of body weight and liver function:Compared with the model group," Qi Yin Three-liang-Three " improved the body weight of model rats and alleviated the increase of 4 biochemical indicators of rat liver function.3.Results of rash,skin moisture and pruritus:Compared with the model group," Qi Yin Three-liang-Three " improved the rash,moisture loss and skin pruritus of model rats.4.Skin epidermal layer thickness and keratinocyte apoptotic protein results:Compared with the model group," Qi Yin Three-liang-Three " reduced the increase in epidermal layer thickness and the expression of Krt-1Experimental conclusion1.By adjusting the dosage and age of the rat model,the weight of the optimized rat model will increase,and the rash will last longer.2." Qi Yin Three-liang-Three " improves the adverse skin reactions in rats.The mechanism of action is related to reducing the thickening of the skin epidermis and reducing the expression of keratinocyte apoptotic protein in the skin.