基于免疫、自噬及肠道菌群探究溃结安康汤治疗溃疡性结肠炎作用机制  

Exploration on the Mechanism of Kuijie Ankang Decoction in Treating Ulcerative Colitis Based on Immune,Autophagy and Intestinal Flora

作　　者：任聪 孟凡艳 弓彦[1] 唐丽利 罗瑞娟 李奕蓁 黎爽 袁程程 柳越冬[3] REN Cong;MENG Fanyan;GONG Yan;TANG Lili;LUO Ruijuan;LI Yizhen;LI Shuang;YUAN Chengcheng;LIU Yuedong(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;Kaifeng Hospital of Traditional Chinese Medicine,Kaifeng 475000,China;The Third Affiliated Hospital of Liaoning University of Traditional Chinese Medicine(Liaoning Anorectal Hospital Hospital),Shenyang 110000,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]开封市中医院,河南开封475000 [3]辽宁中医药大学附属第三医院(辽宁省肛肠医院),辽宁沈阳110000

出　　处：《中国中医药信息杂志》2025年第3期119-128,共10页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(82074449);辽宁省自然科学基金联合基金面上项目(2023-MSLH-188)。

摘　　要：目的探讨溃结安康汤调控免疫、自噬及肠道菌群治疗溃疡性结肠炎的作用机制。方法采用葡聚糖硫酸钠自由饮用建立溃疡性结肠炎小鼠模型,将小鼠随机分为空白对照组、模型组、溃结安康汤组、柳氮磺吡啶(SASP)组和3-甲基腺嘌呤(3-MA)组,每组12只。各给药组分别予相应药液灌胃,空白对照组和模型组予蒸馏水灌胃,连续7 d。观察小鼠一般状况,进行疾病活动指数(DAI)评分,HE染色观察结肠组织形态,ELISA检测结肠组织肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6、IL-8、IL-10含量,RT-qPCR和Western blot分别检测结肠组织LC3、Beclin-1、p62 mRNA及蛋白表达,16S rDNA测序分析肠道菌群结构变化。结果与空白对照组比较,模型组小鼠体质量减少(P<0.05),DAI评分升高(P<0.05),结肠长度缩短(P<0.05),结肠黏膜严重损伤,炎性细胞浸润较明显,结肠组织TNF-α、IL-1β、IL-6、IL-8含量升高(P<0.01),IL-10含量降低(P<0.01),结肠组织LC3和Beclin-1 mRNA表达降低(P<0.05,P<0.01),p62 mRNA和蛋白表达升高(P<0.01),LC3Ⅱ/LC3Ⅰ和Beclin-1蛋白表达降低(P<0.05,P<0.01);与模型组比较,溃结安康汤组、SASP组小鼠体质量增加(P<0.05),DAI评分降低(P<0.05),结肠长度增加(P<0.05),结肠黏膜病理损伤减轻,结肠组织TNF-α、IL-1β、IL-6、IL-8含量降低(P<0.05,P<0.01),IL-10含量升高(P<0.01),结肠组织LC3和Beclin-1 mRNA表达升高(P<0.05,P<0.01),p62 mRNA和蛋白表达降低(P<0.05,P<0.01),LC3Ⅱ/LC3Ⅰ和Beclin-1蛋白表达升高(P<0.05,P<0.01)。16S rDNA测序结果显示,模型组小鼠肠道菌群多样性及均匀度降低,厚壁菌门、放线菌门、Patescibacteria门相对丰度降低(P<0.05),拟杆菌门、疣微菌门、变形菌门相对丰度升高(P<0.05),杆菌纲、红蝽菌纲相对丰度降低(P<0.05),拟杆菌纲、梭状芽孢杆菌纲、疣菌纲相对丰度升高(P<0.05),利吉拉杆菌属、杜波菌属相对丰度降低(P<0.05),未分类的Muribaculaceae属、LachnospiracObjective To investigate the mechanism of Kuijie Ankang Decoction in regulating immune,autophagy and intestinal flora in the treatment of ulcerative colitis(UC).Methods UC mouse model was established by free drinking with sodium dextran sulfate.The mice were randomly divided into blank control group,model group,Kuijie Ankang Decoction group,salazine sulfopyridine(SASP)group and 3-methyladenine(3-MA)group,with 12 mice in each group.Each drug group was given corresponding drugs for gavage,the blank control group and model group were given the same volume of distilled water for gavage for 7 days.The general condition of mice was observed and the disease activity index(DAI)was scored,the morphology of colon tissue was observed by HE staining,the contents of TNF-α,IL-1β,IL-6,IL-8 and IL-10 in colon tissue were detected by ELISA,the mRNA and protein expressions of LC3,Beclin-1 and p62 in colon tissue were detected by RT-qPCR and Western blot,respectively.16S rDNA sequencing was used to analyze the structure of intestinal flora.Results Compared with the blank control group,the mice in the model group showed a decrease in body mass,an increase in DAI score,a decrease in colon length,serious mucosal injury and inflammatory cell infiltration,the contents of TNF-α,IL-1β,IL-6 and IL-8 in colon tissue significantly increased(P<0.05,P<0.01),the content of IL-10 decreased(P<0.01),the mRNA expressions of LC3 and Beclin-1 in colon tissue decreased(P<0.05,P<0.01),the mRNA and protein expression of p62 increased(P<0.01),while the expressions of LC3Ⅱ/LC3Ⅰand Beclin-1 proteins decreased(P<0.05,P<0.01).Compared with the model group,the body mass of mice in Kuijie Ankang Decoction group and SASP group increased(P<0.05),DAI score decreased(P<0.05),the colon length increased(P<0.05),the pathological damage of colon mucosa was alleviated,the contents of TNF-α,IL-1β,IL-6 and IL-8 in colon tissue decreased(P<0.05,P<0.01),the content of IL-10 increased(P<0.01),the expressions of LC3 and Beclin-1 mRNA in colon tissue increased(P<0.0

关 键 词：溃疡性结肠炎 溃结安康汤 肠道菌群 自噬 炎症反应 小鼠 

分 类 号：R285.5[医药卫生—中药学]