熊果酸通过NF-κB信号通路对小鼠结肠炎的作用及机制  

The intervention effect and mechanism of ursolic acid on DSS-induced ulcerative colitis in mice through NF-κB signaling pathway

作　　者：杨艳 李文静 蒯君 郭晓鹤[1] 秦咏梅[1] YANG Yan;LI Wenjing;KUAI Jun;GUO Xiaohe;QIN Yongmei(Department of Gastroenterology,the First Affiliated Hospital of Xinxiang Medical University,Xinxiang 453100,China)

机构地区：[1]新乡医学院第一附属医院消化内科,河南新乡453100

出　　处：《胃肠病学和肝病学杂志》2025年第2期228-232,共5页Chinese Journal of Gastroenterology and Hepatology

基　　金：河南省医学科技攻关计划项目(LHGJ20200502,LHGJ20210539);新乡医学院第一附属医院青年基金项目(QN-2017-B019)。

摘　　要：目的研究熊果酸(ursolic acid,UA)对小鼠溃疡性结肠炎(ulcerative colitis,UC)的治疗作用及对NF-κB信号通路的影响。方法将30只小鼠随机分为5组,每组有6只小鼠,分为正常组、模型组、UA低剂量组(10 mg/kg)、UA中剂量组(20 mg/kg)和UA高剂量组(40 mg/kg)。正常组小鼠正常常规饲养,其余组小鼠连续7 d饮用3%DSS溶液以诱导小鼠实验性结肠炎,造模同时连续7 d分别给予生理盐水和不同浓度的UC腹腔注射,观察各组小鼠一般情况,测量小鼠结肠长度、脾脏重量变化,对小鼠结肠组织进行HE染色,观察小鼠结肠黏膜组织损伤情况,采用ELISA法检测小鼠结肠组织中TNF-α、IL-1β、IL-6、IL-10表达情况,用蛋白免疫印记及免疫组织化学染色实验检测结肠组织内NF-κB p65和p-NF-κB p65水平变化。结果与正常组小鼠相比,模型组小鼠有腹泻、便血和精神萎靡等情况,体质量也显著下降,脾脏重量增加,结肠长度缩短,DAI评分明显升高。给予UA干预后,与模型组相比,UA低剂量组、UA中剂量组和UA高剂量组小鼠结肠炎症明显改善,小鼠结肠组织中TNF-α、IL-1β和IL-6表现水平显著降低,IL-10水平显著升高。UA中剂量、UA高剂量组小鼠p-NF-κB p65蛋白表达水平显著降低。结论UA可能通过抑制NF-κB信号通路改善DSS诱导的小鼠UC的症状和炎症反应。Objective To investigate the therapeutic effect of ursolic acid(UA)on DSS-induced experimental ulcerative colitis(UC)in mice,and the effect on NF-κB signaling pathway.Methods Thirty mice were randomly divided into 5 groups,with 6 mice in each group.They were divided into the normal group,the model group,the low dose group of UA(10 mg/kg),the medium dose group of UA(20 mg/kg)and the high dose group of UA(40 mg/kg).The mice model of UC was established by free drinking of 3%DSS for 7 days.At the same time,the normal saline and UA at different concentrations was administered by intraperitoneal injection for 7 continuous days respectively in other groups of mice besides the normal group.The general conditions of mice in each group were observed,the length of colon and the weight of spleen were measured,and the colon tissues of mice were stained with HE to observe the damage of colonic mucosa.The expressions of TNF-α,IL-1β,IL-6 and IL-10 in colon tissue were detected by ELISA method.The levels of NF-κB p65 and p-NF-κB p65 in colon tissue were detected by Western blotting and immunohistochemical staining.Results The mice in model group showed diarrhea,blood in stool,energetic dispirited,a reduction in body mass,increased spleen weight,shortened colon length,and significantly increased DAI score.However,no relevant manifestations were observed in normal mice.After UA intervention,compared with the model group,the colitis of mice with different doses of UA were significantly improved.Besides,the expression levels of TNF-α,IL-1βand IL-6 in the vehicle group were significantly increased,while the expression level of IL-10 was significantly decreased(P<0.05).In addition,the protein expression levels of p-NF-κB p65 in the medium dose of UA and the high dose of UA group were significantly decreased.Conclusion UA may improve the symptoms and inflammatory response of DSS-induced UC in mice by inhibiting NF-κB signaling pathway.

关 键 词：熊果酸 溃疡性结肠炎 NF-ΚB信号通路 影响机制 小鼠 

分 类 号：R574.62[医药卫生—消化系统]