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环境雌激素壬基酚对雄鼠雌激素及ERβ表达影响

Influence of environmental estrogen nonylphenol on expressions of estrogen and ERβ in male rats
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摘要 目的壬基酚(nolyphenol,NP)是环境雌激素典型代表,其发挥的拟雌激素作用与人类多种癌症的发生关系密切。本研究通过观察NP灌胃暴露对雄性大鼠体内血清E2及盲肠黏膜ERG表达的影响,初步探讨NP与大肠黏膜恶变可能存在的关系。方法60只SD雄性大鼠随机分为5组:即空白对照组(玉米油);阳性对照组[Ez,30mg/(kg·d)]NP低、中、高剂量组(NP灌胃浓度分别为50、100、200rag/(kg·d)]。连续灌胃NP60d后,腹主动脉取血及采集盲肠黏膜组织。直接化学发光法检测大鼠血清中E。水平;荧光定量PCR检测盲肠黏膜组织中ERBmRNA相对表达量;免疫组化检测黏膜组织中ER8蛋白的表达水平。结果与空白对照组(23.25±3.44)pmol/L比较,NP低(28.08±4.89)lomol/L、中(36.53±2.73)9mol/L、高剂量组(47.18±3.04)pmol/L血清E2浓度均升高,且随NP灌胃剂量增大,E。水平升高越明显,P〈0.05;NP低、中、高剂量组ERBmRNA相对表达量分别为(1.23±0.06)、(1.08±0.19)和(1.04±0.11),较空白对照组(1.37±0.01)、阳性对照组(1.80±0.02)比较均下调,且随NP灌胃剂量增加ERGmRNA表达下调更明显,P〈0.05;NP低、中、高剂量组盲肠黏膜中ERB蛋白表达的光密度值分别为(1669.7±144.0)、(1740.0±53.5)和(1647.7±140.2),较阳性对照组(2080.0±188.8)表达降低,且随NP灌胃剂量升高而下降越明显,P〈0.05。结论NP可减低大鼠血清中原有E。水平,但是由于NP具有拟雌激素活性,可能通过竞争抑制作用使大鼠血清E2水平表现为增高,而ERp的基因和蛋白在肠黏膜表达则下调,由于E2及ERB对大肠黏膜具有保护作用,说明NP使E2及ERB对肠黏膜保护作用降低,从而可能增加结肠黏膜恶变的风险。 OBJECTIVE Estrogen (E2) and estrogen receptor (ER) can inhibit the occurrence and progression of colorectal mucosal canceration. Nolyphenol (NP) plays a role similar to E2 and has close association with the occurrence I of multiple cancers in human. This study preliminarily explored the potential relationship between NP and colorectal mu- cosal canceration by observing the influence of exposure to NP gavage on the in-vivo expressions of serum E2 and cecal mucosal ERE in male rats. METHODS A total of 60 SD male rats were randomly divided into 5 groups, namely blank control group (fed by corn oil), positive control group [fed by E2 30 mg/(kg · d)], and low-, middle- and high-dosage NP groups [fed by garage of NP 50, 100 and 200 mg/(kg · d), respectively]. After continuous gavage of NP for 60 d, blood from aorta abdominalis and cecal mucosal tissues were collected. Direct chemiluminescent method was used to detect the level of serum E2 in the rats, while fluorescent quantitative polymerase chain reaction (FQ-PCR) the relative expres- sion of ER mRNA in cecal mucosal tissues, and immunohistochemical method the expression of ER protein in mucosal tissues. RESULTS Compared with blank control group, low (28.08±4.89) pmol/L,middle (36.53±2. 73) pmol/L, and high (47.18±3.04) tomol/L dosage NP groups were evidently higher in the level of serum E2 , and the higher the ga- raged NP dosage was, the more obvious the increase of E2 level became (P〈0.05). Low (1.23±0.06), middle (1.08±0.19) and high (1.04±0. ll)-dosage NP groups were notably lower in the expression of ER[3 mRNA than blank control group (1.37±0.01) and positive control group (1.80±0.02), and the higher the garaged NP dosage was, the more ob- vious the decrease of ERp mRNA expression became (P〈0.05). The optical density values of ERt3 protein expression in cecal mucosa of NP low, medium and high dose groups were respectively: (1 669. 7±144. 0), (1 740. 0± 53. 5), (1 6
作者 杨雪峰 谢铭 宁伟伟 罗娅 许洁 YANG Xue-feng1, XIE Ming1, NING Wei-wei1, LUO Ya2, XU J ie2 (1. Ddepartment of Gastrointestinal Surgery, Affiliated Hospital of Zunyi Medical College, Zunyi 563003, P.R. China 2. School of Public Health, Zunyi Medical College, Zunyi 563000, P. R. China)
出处 《中华肿瘤防治杂志》 北大核心 2017年第18期1275-1279,共5页 Chinese Journal of Cancer Prevention and Treatment
基金 贵州省科学技术基金[黔科合J字(2014)2185号]
关键词 壬基酚 盲肠黏膜组织 雌激素 雌激素受体Β nolyphenol cecal mucosal tissue estrogen estrogen receptorβ
作者简介 杨雪峰,男,布依族,贵州紫云人,硕士,副主任医师,主要从事消化道肿瘤发病机制的研究工作。Tel:86—851—28608241E—mail:yangxuefengl978@126.com;许洁,女,贵州遵义人,博士,教授,主要从事环境毒理与疾病的研究工作。Tel:86—851—28642666E-mail:649904039@qq.com
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