[1]邓 颂,王爱萍,陈 曦,等.黄芪白术汤下调miR-31-5p/STAT3环路抑制结肠炎相关性结肠癌进程[J].中国药理学通报,2019,(09):1308-1313.[doi:10.3969/j.issn.1001-1978.2019.09.023]
 DENG Song,WANG Ai-ping,CHEN Xi,et al.Huangqi Baizhu decoction prevents CAC process by inhibiting miR-31-5p/STAT3 positive circle[J].Chinese Pharmacological Bulletin,2019,(09):1308-1313.[doi:10.3969/j.issn.1001-1978.2019.09.023]
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黄芪白术汤下调miR-31-5p/STAT3环路抑制结肠炎相关性结肠癌进程()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2019年09期
页码:
1308-1313
栏目:
复方药物药理学
出版日期:
2019-09-09

文章信息/Info

Title:
Huangqi Baizhu decoction prevents CAC process by inhibiting miR-31-5p/STAT3 positive circle
文章编号:
1001-1978(2019)09-1308-06
作者:
邓 颂王爱萍陈 曦巫燕莉李燕舞
广州中医药大学脾胃研究所中药药理室,广东 广州 510405
Author(s):
DENG Song WANG Ai-ping CHEN Xi WU Yan-li LI Yan-wu
Pi-Wei Institute, Guangzhou University of Chinese Medicine, Guangzhou 510405,China
关键词:
miR-31-5p STAT3 IL-6 黄芪白术汤 结肠炎相关性结肠癌 白术内酯Ⅱ+黄芪甲苷
Keywords:
miR-31-5p STAT3 IL-6 Huangqi Baizhu decoction colitis-related colon cancer atractylenolide Ⅱ and astragaloside
分类号:
R-332; R289.5; R322.45; R392.12; R574.62; R735.35; R977.6
DOI:
10.3969/j.issn.1001-1978.2019.09.023
文献标志码:
A
摘要:
目的 探讨miR-31-5p/STAT3在结肠炎相关性结肠癌(colitis-associated cancer,CAC)发病机制中的作用,以及黄芪白术汤的干预机制。方法 采用氧化偶氮甲烷(AOM)/葡聚糖硫酸钠(DSS)方法建立C57BL/6小鼠CAC模型,并检测对照组和CAC模型小鼠中microRNA的差异表达。qPCR验证筛选差异microRNA; Western blot检测STAT3、p-STAT3、IL-6Rα的表达水平。结果 一次性腹腔注射AOM,结合3% DSS自由饮用3个循环造模,8周后模型小鼠结肠黏膜出现中、重度异型增生,并伴随大量炎细胞浸润,经检测,CAC小鼠结肠组织中miR-31-5p及STAT3、p-STAT3蛋白的表达明显升高; 黄芪白术汤干预后,miR-31-5p及STAT3、p-STAT3蛋白的表达下调。体外研究表明,RAW264.7细胞转染miR-31-5p precursor后,STAT3蛋白明显增高; 促炎因子IL-6、TNF-α刺激RAW264.7 24 h后,miR-31-5p水平也明显升高,提示炎症因子可引起miR-31-5p/STAT3的正相关上调。同时,白术内酯Ⅱ+黄芪甲苷混合物可明显下调IL-6刺激引起的miR-31-5p、STAT3、IL-6Rα增高。结论 miR-31-5p/STAT3在上皮细胞与免疫细胞之间可能形成一个正反馈的环路,在CAC病理微环境中发挥持续放大炎症效应,最终导致结肠上皮的异型增生,甚至肿瘤发生。
Abstract:
Aim To explore the role of miR-31-5p/STAT3 in the pathogenesis of colitis-assosiated cancer(CAC)and the intervention mechanism of Huangqi Baizhu decoction.Methods The CAC model of C57BL/6 mice was established by AOM/DSS method.The differential expression of microRNA in control and CAC mice was detected.qPCR was used to screen differential microRNAs; Western blot was used to detect the expression levels of STAT3, p-STAT3 and IL-6Rα.Results AOM was injected into abdominal cavity once, combined with 3% DSS free drinking for three cycles to establish model.After eight weeks, moderate and/or severe dysplasia of colonic mucosa appeared in model mice.After detection, the expression of miR-31-5p and STAT3 and p-STAT3 proteins significantly increased.After intervention with Huangqi Baizhu decoction, the expressions of miR-31-5p and STAT3 and p-STAT3 proteins were down-regulated.In vitro, miR-31-5p over-expression in RAW264.7 by transfect method, and the expression of STAT3 protein increased significantly compared with that of control.On the other hand, stimulated by IL-6 or TNF-α for 24 h, miR-31-5p levels were up-regulated significantly, suggesting that inflammatory factors could cause a positive correlation between miR-31-5p/STAT3.At the same time, ATRII+AST(atractylodesin Ⅱ+astragaloside)mixture significantly down-regulated miR-31-5p, STAT3, IL-6Rα increase induced by IL-6 stimulation.Conclusions miR-31-5p/STAT3 forms a positive feedback loop, which plays an important role in the pathogenesis of CAC.miR-31-5p/STAT3 may continue to amplify the inflammation effect and eventually lead to the dysplasia of colonic epithelium and even tumorigenesis.

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备注/Memo

备注/Memo:
收稿日期:2019-05-18,修回日期:2019-06-22
基金项目:国家自然科学基金资助项目(No 81202627)
作者简介:邓 颂(1993-),男,硕士生,研究方向:中药药理学,E-mail:504597827@qq.com;
李燕舞(1976-),女,博士,副研究员,硕士生导师,研究方向:中药药理学,通讯作者,E-mail:liyanwu@gzucm.edu.cn
更新日期/Last Update: 2019-08-14