雌激素膜受体对良性乳腺结构不良性疾病痛觉过敏微环境的影响  

The mechanism of influence of estrogen membrane receptor on hyperpathia microenvironment in patients with benign mammary dysplasia

作　　者：袁晓英 刘畅 杜威 付先芸 YUAN Xiao-ying;LIU Chang;DU Wei;FU Xian-yun(Women and Children Hospital Affiliated to China Three Gorges University,Yichang,Hubei 443000,China)

机构地区：[1]三峡大学附属妇女儿童医院,湖北宜昌443000 [2]三峡大学医学院,湖北宜昌443000

出　　处：《中国临床研究》2018年第11期1463-1466,共4页Chinese Journal of Clinical Research

基　　金：湖北省卫生厅一般科研项目(KJ2017QT007);湖北省宜昌市卫生科技项目(A14301-42)

摘　　要：目的以雌激素膜受体、痛觉过敏微环境及其相互关系为靶点,探讨良性乳腺结构不良发生的可能机制。方法选择2016年6月至12月经病理及彩超同时证实为良性乳腺结构不良的患者44例,光镜HE染色观察病理变化,Western blot方法检测雌激素核受体α(ERα)、雌激素膜受体(G蛋白偶联雌激素受体1,GPER1)、细胞外信号调节激酶(ERK)通路相关蛋白及痛觉过敏微环境中促炎因子的表达水平。结果良性乳腺结构不良患者疼痛总发生率为63. 64%,其中纤维瘤疼痛发生率为66. 67%,纤维囊性变疼痛发生率为16. 67%,合并两种及以上病变疼痛发生率为90. 0%。纤维瘤与纤维囊性变的疼痛发生率比较有统计学差异(P <0. 017),合并两种及以上病变与纤维囊性变的疼痛发生率比较有统计学差异(P <0. 017),纤维瘤与合并两种及以上病变的疼痛发生率比较无统计学差异(P> 0. 017)。疼痛组ERK的表达高于无疼痛组(P <0. 05),其余炎症相关因子[白介素(IL)-1β、肿瘤坏死因子(TNF)-α、神经生长因子(NGF)]组间比较无统计学差异(P> 0. 05)。痛觉过敏微环境中,炎症因子IL-1β与TNF-α存在显著相关性(r=0. 825,P=0. 002),NGF与TNF-α有相关性(r=0. 658,P=0. 028)。两组间ERα表达无统计学差异(P> 0. 05)。GPER1表达在疼痛组低于无疼痛组(P <0. 05)。ERα/GPER1比值在疼痛组高于无疼痛组(P <0. 05)。结论良性乳腺结构不良患者疼痛的发生与病变性质相关。GPER1表达下调导致炎症抑制作用减弱、促炎微环境使外周致敏化是疼痛发生的重要机制。Objective To investigate the possible pathogenesis of benign breast dysplasia by taking estrogen membrane receptor,hyperpathia microenvironment and their interrelation as the research targets. Methods Forty-four patients with benign breast dysplasia confirmed by pathology and color doppler ultrasound between June 2016 and December 2016 were selected. Pathological changes of breast were observed by HE staining and light microscopy. Western blot method was used to detect the expression levels of related proteins of estrogen nuclear receptor（Era）-estrogen membrane receptor 1[G protein-coupled estrogen receptor 1（GPER1）]-extracellular signal regulated kinase（ERK） pathway and pro-inflammatory factors in hyperpathia microenvironment. Results The total incidence of pain was 63. 64% in patients with benign breast dysplasia in which the incidence of pain was 66. 67% for fibroma,16. 67% for fibrocystic lesions and 90. 0% for combined lesions of two or more. There were significant differences in incidences of pain between fibroma and fibrocystic lesions（P〈0. 017） and between combined lesions of two or more and fibrocystic lesions（P〈0. 017）,while there was no significant difference in incidences of pain between fibroma and combined lesions of two or more（P〉0.017）. The expression level of ERK in pain group was significantly higher than that in no pain group（P〈0. 05）,while there were no significant differences in other inflammatory related factors including interleukin（IL）-1β,tumor necrosis factor（TNF）-α and nerve growth factor（NGF） among groups（all P〉0. 05）. In hyperpathia microenvironment,there were significant correlations between IL-1β and TNF-α（r = 0. 825,P = 0. 002） and between NGF and TNF-α（r = 0. 658,P = 0. 028）. There was no significant difference in expression level of ERα between pain group and no pain group（P〉0. 05）,while the expression level of GPER1 in pain group was significantly lower than that in no pain group,thus the ratio of ERα/GPER

关 键 词：良性乳腺结构不良 雌激素膜受体 雌激素核受体 细胞外信号调节激酶通路 痛觉过敏微环境 

分 类 号：R655.8[医药卫生—外科学]