摘要
目的通过表皮生长因子受体抑制剂(epidermal growth factor receptor inhibitors,EGFRIs)——厄洛替尼干预小鼠,与P物质(substance P,SP)致瘙痒小鼠进行对比性研究,探索瘙痒的发生机制。方法两组小鼠分别予厄洛替尼和SP致痒,观察小鼠的行为学表现和皮肤表观状态;取小鼠皮肤,比较二者的皮肤病理形态,免疫组化法检测小鼠皮肤中NK-1R的表达;ELISA检测小鼠外周血中白介素(interleukin,IL)-31、IL-33、组胺、白三烯B4、SP的浓度,比色法检测一氧化氮(NO)的浓度。结果厄洛替尼致痒表现在给药2~5 d一过性瘙痒,而SP致痒表现在给药后1 h瘙痒明显,逐渐缓解,二者的搔抓表现一致;两种致痒各组间IL-31、IL-33、组胺、白三烯、SP差异有显著性(P<0.05),且部分神经递质的表达趋势表现出一定的相似性。厄洛替尼致痒小鼠和SP致痒小鼠皮肤NK-1R免疫组化呈阳性,分布情况一致。结论厄洛替尼所致皮肤瘙痒可能与SP/NK-1R的结合有关,通过下游的信号因子致痒。
Objective The aim of this study was to investigate the mechanism underlying pruritus by comparing the epidermal growth factor receptor inhibitor（EGFRI）-erlotinib mouse model with the substance P（SP）-induced pruritus mouse model. Methods Two randomized groups of mice were treated with erlotinib or SP to induce pruritus. Behavioral and skin manifestations were observed. Pathological images and neurokinin 1 receptor（NK-1 R） expression of the skin were determined. Concentration of interleukin（IL）-31,IL-33,histamine,leukotriene B4,and SP was analyzed by enzymelinked immunosorbent assay. Nitric oxide was analyzed by colorimetry. Results Transient pruritus induced by erlotinib appeared 2 to 5 days after treatment. In contrast,continuous pruritus was observed during the first hour,but was then gradually relieved. These two shared similar scratching behavior. Concentration of neurotransmitters showed similar trends in changes among the erlotinib group and SP group. Immunohistochemical expression was also consistent between the erlotinib group and SP group. Conclusions Erlotinib-associated pruritus is related to release of signaling factors through the SP/NK-1 R signaling pathway.
作者
彭艳梅
刘青
邓博
崔慧娟
段桦
邱钰芹
PENG Yanmei;LIU Qing;DENG Bo;CUI Huijuan;DUAN Hua;QIU Yuqin(Beijing University of Chinese Medicine,Beijing 100029,China;China？Japan Friendship Hospital,Beijing 100029)
出处
《中国比较医学杂志》
CAS
北大核心
2018年第5期28-33,共6页
Chinese Journal of Comparative Medicine
基金
北京市科委"首都特色应用研究"专项(编号:Z151100004015168)
国家自然基金青年项目(编号:81603462)
关键词
表皮生长因子受体抑制剂
皮肤不良反应
P物质
NK-1R
阿瑞匹坦
epidermal growth factor receptor inhibitors
EGFRIs
dermatologic adverse effect
substance P
NK-1R
aprepitant
