山东医药2023,Vol.63Issue(35):34-38,5.DOI:10.3969/j.issn.1002-266X.2023.35.008
阿司匹林对表皮生长因子受体酪氨酸酶抑制剂诱导小鼠皮疹的改善作用及其机制
Effect of aspirin in relieving skin rashes induced by EGFR-TKI in mice and the mechanism
摘要
Abstract
Objective To investigate the effect of aspirin in relieving skin rashes induced by epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI)in mice and the possible mechanism.Methods Fifty male Balb/c mice were randomly divided into the control group,model group,and high-dose,medium-dose,and low-dose aspirin groups,with 10 mice in each group.The skin rash models were established by administering the EGFR-TKI erlotinib to the mice in all the groups except the control group.After successful modeling,the mice in the high-,medium-,and low-dose aspirin groups were given aspirin at doses of 1.13,0.75,and 0.38 mg per mouse,respectively,while the mice in the control group were given distilled water at 100 mg/kg,all by gavage,once a day,for a total of 30 days.All the mice were moni-tored for feeding,drinking,urination,defecation,and mental status as well as pruritus and other skin conditions.The skin moisture level was measured using a skin moisture analyzer,and skin inflammation was scored.After the mice were sacrificed,the back skin was taken for observing the pathological changes with HE staining,and serum levels of tumor ne-crosis factor-α(TNF-α)and interleukin-1β(IL-1β)were determined by ELISA.Results In the control group,the skin and general conditions were normal;the mice in the model and low-dose aspirin groups developed skin rashes,scabs,and desquamation on the back,and began to have reduced food intake,increased water intake,increased urination,and re-duced defecation since the first week,accompanied by anxiety and back scratching;compared with the model group,the medium-and high-dose aspirin groups showed significant improvements in skin rashes,scabs,and desquamation,and gradually returned to normal dieting since the second week.Only the model group had mild pruritus,while the other groups did not have any pruritus.No abnormal changes were found in any epidermal layer of the skin tissues in the control group;the model group showed epidermal thickening and substantial inflammatory cell infiltration in the dermis;the high-dose and medium-dose aspirin groups showed slight epidermal thickening and mild inflammatory cell infiltration in the su-perficial dermis,while the low-dose aspirin group had a larger number of inflammatory cells in the superficial dermis;the levels of inflammation in the three aspirin groups were all lower than that in the model group.There was no significant dif-ference in the skin moisture level between the groups(P<0.05).The rash site,desquamation,exudation,skin thickening score,and serum levels of TNF-α and IL-1β were as follows:the control group<the high-dose aspirin group<the medium-dose aspirin group<the low-dose aspirin group and model group(all P<0.05).Conclusion Aspirin can alleviate EG-FR-TKI-induced skin rashes in mice,possibly through reducing serum TNF-α and IL-1β levels and thereby inhibiting in-flammatory response.关键词
阿司匹林/表皮生长因子受体酪氨酸酶抑制剂/炎症因子/皮疹Key words
aspirin/epidermal growth factor receptor-tyrosine kinase inhibitor/inflammatory factor/skin rash分类
医药卫生引用本文复制引用
焦敏,滕威,沈皓,龚福恺,于鲁海,吴建华..阿司匹林对表皮生长因子受体酪氨酸酶抑制剂诱导小鼠皮疹的改善作用及其机制[J].山东医药,2023,63(35):34-38,5.基金项目
新疆维吾尔自治区自然科学基金资助项目(2022D01C136) (2022D01C136)
新疆维吾尔自治区人民医院院内项目(20220128). (20220128)