Establishment Of An Animal Model Of Adverse Reactions Such As Epidermal Growth Factor Receptor Inhibitor-associated Rash

This thesis consists of two parts:a literature review and an animal experiment.The literature review focuses on illustrating links between the occurrence of adverse reactions such as skin rash and targeted drugs(mainly Erlotinib)as well as its close relation to malignancy,trying to figure out the mechanism of Erlotinib-induced rashes,along with both Chinese and Western treatment method for it.Another part is about the animal experiment.3 groups of mice were fed in batches,skin and blood was sampled after the experiment,and a successful establishment of an EGFRIs associated rash animal model was determined by observing and testing changes in skin tissue and hematologic indications before and after the application of Erlotinib.Objective:Erlotinib(Trade Name:Tarceva)is a widely-used targeted drug for non-small cell lung cancer(NSCLC)in recent years,which brings curative effects,together with many side effects such as rashes,the most common and unbearable one.The aim of this study is to observe and test changes in epidermis,pathology,hematologic indications and other aspects before and after the application of Erlotinib in mice and to copy and build the rash animal models caused by Erlotinib so as to provide models for evaluating the efficacy of topical medications for rash.Methods:Some BALB/c female mice were randomly divided into experimental group and control group(Different experimental batches have different feeding cycles for comparison).The experimental group were given 100 mg/kg dosage of Erlotinib with a concentration of 10 g/L by gavage while the control group dealt with an equal volume of deionized water by gavage once daily.Hairs of the head,neck and the back of each mouse was removed 24 hours prior to drug intervention(Different experimental batches were provided with no hair removal group,different time hair removal group for comparison).At the end of the experiment,the skin in the neck,the back and waist,and blood in heart tip would be fetched for observing and testing the differences between the experimental group and the control group in mice skin,biopsy,blood biochemical indicators and the like.3 experiments were carried out to ensure the repeatability of the experiment.Results:There are statistically significance(P<0.05)between experimental group and control group in the following aspects,which are 'days for hair regrowth','days of hair complete regrowth','desquamation time' 'time when the rash appears','the number of pore expansion and the level of IL-1B,IL-2R,IL-6,IL-30,TNF-a,IgA,IgG and IgM'.There are statistically significance(P<0.05)between different time of experimental group in the following aspects,which are 'days for hair regrowth','days of hair complete regrowth and the level of IL-1B,IL-2R,IL-6,IL-30 and TNF-?'.These indicators increased with the increase of medication time(P<0.05)and reached the peak on the 21st day.There are statistically significance(P<0.05)between different time of experimental group in the following aspects,which are 'the level of IgA,IgG and IgM'.These indicators reached the peak on the 14th day.There are no statistically significance(P>0.05)between different time of experimental group in the following aspects,which are 'desquamation time','time when the rash appears and the number of pore expansion'.Conclusion:(1)This experiment is consistent with many researchers' point of the view that'the rash induced by EGFRIs is an inflammatory response'.(2)The inflammatory response of mice caused by Erlotinib was more severe as time flows;The mice given Erlotinib may have an immune response which may based on the inflammatory reaction.(3)This EGFRIs-induced rash mouse model is proved reliable,practical and reproducible and could be further adopted or even be popularized for clinical,experimental and institutional uses.