槲皮素调控白细胞介素-6/信号转导及转录激活蛋白3信号通路在结肠炎性相关结肠癌小鼠模型的机制研究  

Quercetin regulates IL-6/STAT3 signaling pathway in mouse models of inflammation-related colon cancer:a mechanistic study

作　　者：蔡剑辉[1] 任约翰[1] 厉金雷[1] 倪士昌[1] Cai Jianhui;Ren Yuehan;Li Jinlei;Ni Shichang(Department of Colorectal Surgery,the First Affiliated Hospital of Wenzhou Medical University,Zhejiang 325000,China)

机构地区：[1]温州医科大学附属第一医院结直肠肛门外科,325000

出　　处：《中国药物与临床》2020年第6期896-899,共4页Chinese Remedies & Clinics

基　　金：浙江省温州市基础性医疗卫生科技项目(Y20190758)。

摘　　要：目的 探究槲皮素调控白细胞介素(IL)-6/信号转导及转录激活蛋白3(STAT3)信号通路在结肠炎性相关结肠癌小鼠模型中的作用及其机制。方法 采用氧化偶氮甲烷(AOM)联合葡聚糖硫酸钠(DSS)诱导结肠炎性相关的结肠癌小鼠模型,将40只C57BL/6小鼠随机分为对照组、模型组、槲皮素低剂量及高剂量组,以30 mg/kg、100 mg/kg槲皮素灌胃处理小鼠,连续灌胃4周,其他组别以0.9%氯化钠注射液替代;观察各组小鼠的一般情况,采用苏木精-伊红(HE)染色观察小鼠结肠组织病理变化,TUNEL检测法检测小鼠结肠组织细胞凋亡情况,免疫组织化学法检测小鼠结肠组织中细胞核相关抗原(Ki67)的表达,酶联免疫吸附试验(ELISA)法检测血清中细胞因子的分泌情况,蛋白质印迹法检测结肠组织中信号STAT3的表达。结果 与模型组相比,槲皮素组小鼠体质量、总结肠长度及凋亡细胞数明显增加,肿瘤个数、炎性评分、增殖评分、Ki67的表达、肿瘤坏死因子(TNF)-α、干扰素(IFN)-γ、IL-6、IL-17及STAT3磷酸化水平显著下降(P<0.05),且高剂量组作用效果更显著。结论 槲皮素可能下调IL-6/STAT3信号通路的活性,减少炎性因子水平,阻碍肿瘤细胞的增殖,促进肿瘤细胞的凋亡,从而保护结肠炎性相关结肠癌小鼠组织损伤。Objective To investigate the role and mechanism of quercetin regulating IL-6/nuclear transcription factor and transcriptional activator 3(STAT3)signaling pathway in mouse models of inflammation-related colon cancer.Methods The mice models of acute colitis related colon cancer were induced by azoxymethane(AOM)combined with dextra sulfate sodium(DSS).Forty C57BL/6 mice were randomly divided into control group,model group,low-dose and high-dose quercetin groups.The quercetin groups were intragastrically treated with 30 mg/kg and 100 mg/kg quercetin for 4 weeks.The other groups received gavage of normal saline.The general conditions of mice in each group were observed.The pathological changes of colon tissue were studied by HE staining.The apoptosis of colon tissue cells was detected by TUNEL method.The expression of nuclear related antigen(Ki67)in colon tissue was detected by immunohistochemistry.The secretion of serum cytokines(TNF-α,IFN-γ,IL-6,and IL-17)was detected by ELISA.The expression of STAT3 in colon tissue was detected by Western bloting.Results Compared with model group,the quercetin groups showed significantly increased weight,total colon length,and number of apoptotic cells but lower number of tumor,scores of inflammatory and proliferation,expression of Ki67,TNF-α,IFN-γ,IL-6,and IL-17,and phosphorylation level of STAT3(P<0.05).The difference was more significant in high-dose quercetin group.Conclusion Quercetin may down-regulate activity of IL-6/STAT3 signaling pathway,reduce levels of inflammatory factors,inhibit proliferation and promote apoptosis of tumor cells,thus protecting against tissue damage in mice with inflammation-related colon cancer.

关 键 词：槲皮素 白细胞介素6 信号传导 小鼠 STAT3 炎症相关结肠肿瘤 

分 类 号：R285.5[医药卫生—中药学]