文章摘要
屈芸,朱磊,王琼,王耀辉,胡静怡,连紫宇,吉跃进,周恩,沈洪.清肠化湿方通过激活AhR/IL-22缓解小鼠溃疡性结肠炎的作用机制研究[J].南京中医药大学学报,2021,37(6):823-829.
清肠化湿方通过激活AhR/IL-22缓解小鼠溃疡性结肠炎的作用机制研究
Research on the Effect and Mechanism of Qingchang Huashi Recipe on Relieving Colitis in Mice through AhR/IL-22
  
DOI:
中文关键词: 关键词:溃疡性结肠炎  清肠化湿方  芳香烃受体  白细胞介素-22
英文关键词: ulcerative colitis  Qingchang Huashi Recipe  AhR  IL-22
基金项目:
作者单位
屈芸,朱磊,王琼,王耀辉,胡静怡,连紫宇,吉跃进,周恩,沈洪 南京中医药大学附属医院/江苏省中医院江苏 南京 210029 
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中文摘要:
      目的 通过构建溃疡性结肠炎(Ulcerative colitis,UC)小鼠模型,从芳香烃受体(AhR)角度,观察清肠化湿方对白细胞介素-22(IL-22)分泌及黏蛋白-2(MUC-2)与紧密连接蛋白(Claudin4)表达的作用,阐述其缓解小鼠UC的作用机制。方法 用DSS构建UC小鼠模型,每日观察小鼠体质量、粪便形状、隐血情况,同时进行疾病活动指数(DAI)评分。给药结束后测量小鼠结肠长度,HE染色观察结肠病理情况,qPCR检测结肠组织白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、AhR的mRNA。Western blot检测结肠MUC-2、AhR、细胞色素P4501A1酶(CYP1A1)、IL-22、Claudin4表达水平。结果 与正常组比较,模型组小鼠DAI评分上升(P<0.01),结肠长度缩短(P<0.01),结肠黏膜病理受损情况严重;AhR的mRNA表达下降(P<0.05),IL-1β、TNF-α、IL-6的mRNA表达上升(P<0.05,P<0.01);MUC-2、AhR、CYP1A1、IL-22、Claudin4蛋白表达下降(P<0.05,P<0.01)。与模型组比较,美沙拉嗪组、清肠化湿方组DAI评分降低(P<0.01),结肠长度变长(P<0.01),结肠黏膜病理情况改善;IL-1β、TNF-α、IL-6的mRNA表达下降(P<0.05,P<0.01);MUC-2、CYP1A1、Claudin4蛋白表达升高(P<0.01)。与模型组比较,清肠化湿方组AhR的mRNA表达上升(P<0.05),AhR、IL-22蛋白表达升高(P<0.01)。与清肠化湿方组比较,清肠化湿方+TMF组小鼠DAI评分上升(P<0.01);结肠长度缩短(P<0.05);结肠黏膜病理受损情况严重;IL-1β、TNF-α、IL-6的mRNA表达上升(P<0.01);MUC-2、AhR、CYP1A1、IL-22、Claudin4蛋白表达下降(P<0.01)。结论 清肠化湿方能够激活AhR,上调CYP1A1表达,促进IL-22生成,抑制炎症水平,同时增加MUC-2及Claudin4的表达,从而缓解UC。
英文摘要:
      OBJECTIVE To explore the therapeutic effect of Qingchang Huashi recipe on colitis model mice, and explore from the perspective of aromatic hydrocarbon receptor(AhR), to explore the effect of Qingchang Huashi recipe on IL-22 secretion and mucin and tight junction protein expression, and to explain alleviate the mucosal damage mechanism of colitis model mice, so as to provide objective basis for clinical application and drug research and development. METHODS The mouse model of colitis was established by DSS, the body mass, fecal shape, occult blood and DAI score of disease activity index were observed every day. The colon length of mice was measured after administration, and the colonic pathology was observed by HE staining. qPCR was used to detect the mRNA of IL-1β, TNF-α, IL-6 and AhR in colon tissue. The expression levels of colonic mucin(MUC-2), AhR, cytochrome 4501A1(CYP1A1), interleukin-22(IL-22) and tight junction protein (Claudin4) were detected by Western blot. RESULTS Compared with the normal group, the DAI score of the model group increased(P<0.01), the length of colon shortened(P<0.01), the pathological damage of colonic mucosa was severe, the mRNA expression of AhR decreased(P<0.05), the mRNA expression of IL-1 β, TNF-α and IL-6 increased (P<0.05, P<0.01). The expressions of MUC-2, AhR, CYP1A1, IL-22 and Claudin4 decreased(P<0.05). Compared with the model group, the DAI score of mesalazine group and Qingchang Huashi Recipe group decreased(P<0.01), the length of colon lengthened(P<0.01), the pathological condition of colonic mucosa improved, the mRNA expression of IL-1β,TNF-α and IL-6 decreased (P<0.05, P<0.01). The expressions of MUC-2, CYP1A1, Claudin4 protein increased(P<0.01). Compared with the model group, the mRNA expression of AhR increased(P<0.05). The expression of AhR and IL-22 protein in Qingchang Huashi Recipe group increased(P<0.01). Compared with the Qingchang Huashi Recipe group, the DAI score of the Qingchang Huashi Recipe+TMF group increased(P<0.01), the length of colon was shortened(P<0.05), the pathological damage of colonic mucosa was serious, the mRNA expression of IL-1β, TNF-α, IL-6 increased(P<0.01), the expressions of MUC-2, AHR, CYP1A1, IL-22 and Claudin4 decreased(P<0.01).CONCLUSION Qingchang Huashi Recipe can activate AhR, to up-regulate CYP1A1 protein, promote the production of IL-22, inhibit the level of inflammation, increase the expression of mucin and tight junction protein, and relieve colitis.
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