基于芳香烃受体探讨青黛及其主要成分缓解溃疡性结肠炎的作用机制  

Discussion on the Mechanism of Indigo Naturalis and Its Main Components in Relieving Ulcerative Colitis Based on Aryl Hydrocarbon Receptor

作　　者：高阳 顾思臻 薛艳 刘晓雯 窦丹波[1] GAO Yang;GU Sizhen;XUE Yan;LIU Xiaowen;DOU Danbo(Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Yangzhi Rehabilitation Hospital,Tongji University,Shanghai 201619,China)

机构地区：[1]上海中医药大学附属曙光医院,上海201203 [2]同济大学附属养志康复医院,上海201619

出　　处：《中国中医药信息杂志》2023年第11期126-131,共6页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金(82174288、81804037);上海市科委科技创新行动计划生物医药科技支撑专项(22S21903500);上海市科委科技创新行动计划医学创新研究专项(20Y21901900);上海市卫生行业临床研究专项(20184Y0047);上海市“医苑新星”青年医学人才培养项目(2019年);上海中医药大学“杏林学者”(2020年);上海中医药大学附属曙光医院四明临床专项(SGKJLC-202029);ICD-11传统医学章节推广应用体系建设项目[ZY(2021-2023)-0213]。

摘　　要：目的探讨青黛及其主要成分对溃疡性结肠炎(UC)小鼠的治疗作用及机制。方法将42只SPF级雄性C57BL/6小鼠随机分为空白组、模型组、青黛组、靛蓝组、靛玉红组和色胺酮组,每组7只。除空白组外,其余组采用葡聚糖硫酸钠自由饮用10 d建立UC小鼠模型,各给药组从造模第4日开始予相应药液灌胃,连续7 d。记录小鼠一般状况,测量小鼠结肠长度,HE染色观察结肠组织病理形态,Western blot检测结肠组织芳香烃受体(AHR)、细胞色素P4501A1(CYP1A1)、白细胞介素(IL)-10、IL-22蛋白表达量,RT-PCR检测结肠组织AHR、CYP1A1、IL-10、IL-22 mRNA表达。结果与空白组比较,模型组小鼠体质量明显减轻,结肠长度明显缩短;结肠组织结构破坏,隐窝结构变形,上皮细胞坏死水肿,中性粒细胞和淋巴细胞弥漫性浸润,结肠组织CYP1A1、IL-10、IL-22蛋白表达明显降低,AHR、IL-10、IL-22 mRNA表达明显降低,差异均有统计学意义(P<0.01)。与模型组比较,各给药组小鼠体质量明显增加(P<0.01),青黛组、靛玉红组和色胺酮组小鼠结肠长度明显增加(P<0.05,P<0.01);各给药组小鼠结肠组织黏膜损伤及溃疡情况明显好转,水肿及炎性细胞浸润不同程度改善,结肠组织AHR、CYP1A1、IL-10、IL-22蛋白表达明显升高(P<0.01),靛玉红组和色胺酮组小鼠结肠组织AHR、CYP1A1、IL-10、IL-22 mRNA表达明显升高(P<0.01)。结论青黛可能通过激活AHR/CYP1A1信号途径调节炎症因子IL-10、IL-22表达,从而改善UC小鼠炎症损伤。Objective To investigate the therapeutic effects and mechanism of Indigo Naturalis and its main components on ulcerative colitis(UC)mice.Methods Totally 42 SPF male C57BL/6 mice were randomly divided into blank group,model group,Indigo Naturalis group,indigo group,indirubin group,and tryptanthrin group,with 7 mice in each group.Except for the blank group,the other groups were used to establish UC mouse models by freely drinking dextran sodium sulfate for 10 days.Each treatment group was given corresponding drug solution by gavage from the 4th day of modeling for 7 consecutive days.General conditions of the mice were recorded,the length of colon was recorded,the pathological changes of colon tissue were observed by HE staining,and the expressions of AHR,CYP1A1,IL-10,IL-22 in colon tissue were detected by Western blot,the mRNA expressions of AHR,CYP1A1,IL-10 and IL-22 were detected by RT-PCR.Results Compared with the blank group,the body mass of the model group mice were significantly reduced,and the colon length was significantly shortened;the structure of colon tissue was damaged,crypt structure was deformed,epithelial cells were necrotic and edematous,neutrophils and lymphocytes were diffusely infiltrated,the expressions of CYP1A1,IL-10 and IL-22 proteins in colon tissue were significantly decreased,the expressions of AHR,IL-10 and IL-22 mRNA significantly decreased,with statistical significance(P<0.01).Compared with the model group,the body mass of mice in each treatment group significantly increased(P<0.01),while the colon length of mice in Indigo Naturalis group,indirubin group and tryptanthrin group significantly increased(P<0.05,P<0.01);the mucosal damage and ulcers in colon tissue of mice in each treatment group were significantly improved,edema and inflammatory cell infiltration were improved to varying degrees,and the expression of AHR,CYP1A1,IL-10 and IL-22 proteins in colon tissue significantly increased(P<0.01),the expressions of AHR,CYP1A1,IL-10 and IL-22 mRNA in colon tissue of mice in indirubin gro

关 键 词：溃疡性结肠炎 青黛 靛蓝 靛玉红 色胺酮 芳香烃受体 细胞色素P4501A1 小鼠 

分 类 号：R285.5[医药卫生—中药学]