鹰嘴豆芽素A对小鼠溃疡性结肠炎的保护作用及其机制  

Protective effect of biochanin A against ulcerative colitis in mice

作　　者：颜维艳 汪竹芸 蔺晓菁 秦光成[1] 李兴旺 肖晓秋[1] 侯毅 Yan Weiyan;Wang Zhuyun;Lin Xiaojing;Qin Guangcheng;Li Xingwang;Xiao Xiaoqiu;Hou Yi(The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases,the First Affiliated Hospital of Chongqing Medical University;Department of Obstetrics,the First Affiliated Hospital of Chongqing Medical University;Laboratory of Traditional Chinese Medicine,Experimental Teaching and Management Center,Chongqing Medical University)

机构地区：[1]重庆医科大学附属第一医院重大代谢性疾病转化医学重点实验室,重庆400016 [2]重庆医科大学附属第一医院产科,重庆400016 [3]重庆医科大学实验教学管理中心中医药实验室,重庆400016

出　　处：《重庆医科大学学报》2025年第3期331-336,共6页Journal of Chongqing Medical University

摘　　要：目的:研究鹰嘴豆芽素A(biochanin A,BCA)是否对葡聚糖硫酸钠(dextran sulfate sodium salt,DSS)诱导的小鼠溃疡性结肠炎(ulcerative colitis,UC)具有保护作用。方法:将36只C57BL/6N小鼠随机分为正常对照组、DSS模型组、柳氮磺胺吡啶(sulfasalazine,SASP)阳性药物对照组、BCA干预组(5、10、20 mg/kg)。使用2.5%DSS水溶液诱导7 d建立小鼠UC模型,实验期间正常对照组和模型组均每日灌胃0.5%羧甲基纤维素钠(carboxymethyl cellulose sodium,CMC-Na)溶液,阳性对照组给予100 mg/kg SASP,BCA干预组则分别给予5 mg/kg、10 mg/kg和20 mg/kg的BCA混悬液,持续给药10 d,每天记录小鼠体质量变化、粪便状况,最后解剖收集结肠,测量结肠长度,通过苏木精-伊红(hematoxylin-eosin staining,HE)染色对结肠组织进行病理形态检测,实时荧光定量PCR(quantitative real-time PCR,qPCR)方法检测结肠中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)和白细胞介素-10(interleukin-10,IL-10)的水平,免疫荧光检测结肠中紧密连接蛋白闭锁小带蛋白1(zonula occludens 1,ZO-1)和Occludin的表达。结果:5 mg/kg和10 mg/kg BCA能明显缓解UC小鼠体质量减轻,5 mg/kg、10 mg/kg和20 m/kg BCA均能降低疾病活动指数(disease activity index,DAI)评分,且BCA显示出与SASP相似的改善UC小鼠结肠结构和减少结肠缩短的作用。BCA低中高剂量组与模型组相比TNF-α(P=0.024、P=0.060、P=0.003)和IL-6(P=0.002、P<0.001、P<0.001)水平明显降低,IL-10水平明显升高(P=0.006、P=0.003、P<0.001),BCA各组均能不同程度地上调UC小鼠紧密连接蛋白的表达。结论:BCA能有效缓解DSS诱导的小鼠UC症状,减轻小鼠肠道损伤及保护小鼠肠道屏障功能。Objective:To investigate whether biochanin A(BCA)has a protective effect against dextran sodium sulfate(DSS)-induced ulcerative colitis(UC)in mice.Methods:Thirty C57BL/6N mice were randomly divided into normal control group,DSS model group,sulfasalazine(SASP)-positive drug control group,and low/medium/high-dose(5 mg/kg,10 mg/kg,and 20 mg/kg)BCA groups.The mouse model of UC was induced by administering 2.5%DSS aqueous solution for 7 days.During the experimental period,both the normal control and model groups were given 0.5% carboxymethyl cellulose sodium solution daily by gavage.The positive control group was given 100 mg/kg SASP,while the BCA groups were given BCA suspensions at doses of 5 mg/kg,10 mg/kg,and 20 mg/kg.The administration lasted for 10 days.Body weight changes and fecal status of the mice were recorded every day;the colon was dissected,collected,and measured for its length.The colon was stained with Hematoxylin-Eosin for pathomorphological study.Quantitative polymerase chain reaction was used to determine the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-10(IL-10)in the colon.Immunofluorescence was used to determine the expression of tight junction proteins,zonula occluden-1(ZO-1)and occludin,in the colon.Results:It showed that 5 mg/kg and 10 mg/kg BCA significantly alleviated weight loss in mice with UC,while 5 mg/kg,10 mg/kg,and 20 mg/kg BCA reduced the disease activity index scores.Additionally,BCA showed similar effects to SASP in improving the structure and reducing the shortening of the colon in mice with UC.Compared with the model group,all BCA groups had significantly decreased TNF-α(P=0.024、P=0.060、P=0.003)and IL-6(P=0.002、P<0.001、P<0.001)and significantly increased IL-10(P=0.006、P=0.003、P<0.001),with varying degrees of up-regulated expression of tight junction proteins.Conclusion:BCA can effectively alleviate DSS-induced symptoms,reduce intestinal damage,and protect the intestinal barrier in mice with UC.

关 键 词：鹰嘴豆芽素A 溃疡性结肠炎 炎症因子 肠道屏障 

分 类 号：R965[医药卫生—药理学]