安肠愈疡汤对溃疡性结肠炎大鼠结肠组织中TFF3、MUC2和TLR4基因表达的影响*

迟莉丽1#袁浩1宋钦兰1程艳1孙大娟1闫华1王帅1梁峻尉1张晶晶2

山东中医药大学附属医院脾胃病科1(250011)山东中医药大学中西医结合专业2

背景：TLR4可介导免疫和炎症反应，TFF3、MUC2为肠黏膜保护因子，维持肠黏膜屏障功能。目的：观察安肠愈疡汤对溃疡性结肠炎大鼠结肠组织中TFF3、MUC2和TLR4基因表达的影响。方法：应用TNBS制备溃疡性结肠炎大鼠模型。将90只Wistar大鼠随机分为空白对照组、模型组、安肠愈疡汤低、中、高剂量组和美沙拉嗪组，分别给予蒸馏水、不同剂量安肠愈疡汤和美沙拉嗪。21 d后处死大鼠，行结肠黏膜组织病理学评分，采用RT-PCR法检测结肠组织中TFF3、MUC2和TLR4基因表达。结果：与模型组相比，安肠愈疡汤中、高剂量组和美沙拉嗪组组织病理学评分、TLR4表达均显著降低(P<0.05)，TFF3、MUC2表达均显著升高(P<0.05)。与安肠愈疡汤中剂量组相比，安肠愈疡汤高剂量组和美沙拉嗪组组织病理学评分显著降低(P<0.05)，TFF3表达显著升高(P<0.01)。与安肠愈疡汤中剂量组和美沙拉嗪组相比，安肠愈疡汤高剂量组MUC2表达显著升高(P<0.01)，TLR4表达显著降低(P<0.01)。结论：安肠愈疡汤可明显促进溃疡性结肠炎大鼠结肠黏膜修复，其作用机制可能与上调TFF3和MUC2基因表达以及下调TLR4基因表达有关。

关键词结肠炎，溃疡性；安肠愈疡汤；三叶因子3；黏蛋白2；Toll样受体4；治疗

Effect of Anchang Yuyang Decoction on Colon Tissue TFF3, MUC2 and TLR4 Gene Expressions in Rats with Ulcerative Colitis

CHILili1,YUANHao1,SONGQinlan1,CHENGYan1,SUNDajuan1,YANHua1,WANGShuai1,LIANGJunwei1,ZHANGJingjing2.1DepartmentofGastroenterology,AffiliatedHospitalofShandongUniversityofTraditionalChineseMedicine,Jinan(250011);2IntegratedTraditionalandWesternMedicine,ShandongUniversityofTraditionalChineseMedicine,Jinan

Background: TLR4 can mediate immune and inflammatory responses, TFF3, MUC2 are the intestinal mucosa protection factor and can maintain the intestinal barrier function. Aims: To investigate the effect of Anchang Yuyang decoction on colon tissue TFF3, MUC2 and TLR4 gene expressions in rats with ulcerative colitis. Methods: TNBS was used to establish ulcerative colitis model in rats. Ninety Wistar rats were randomly divided into normal control group, model group, low, moderate and high dose Anchang Yuyang decoction groups and mesalazine group, and distilled water, different concentrations of Anchang Yuyang decoction and mesalazine were given respectively. All the rats were sacrificed after 21 days. Colonic histopathological score was assessed, and RT-PCR was used to detect gene expressions of colon tissue TFF3, MUC2 and TLR4. Results: Compared with model group, histopathological score and TLR4 expression were significantly decreased in moderate, high dose Anchang Yuyang decoction groups and mesalazine group (P<0.05), expressions of TFF3 and MUC2 were significantly increased (P<0.05). Compared with moderate dose Anchang Yuyang decoction group, histopathological score in high dose Anchang Yuyang decoction group and mesalazine group was significantly decreased (P<0.05), and TFF3 expression was significantly increased (P<0.01). Compared with moderate dose Anchang Yuyang decoction group and mesalazine group, MUC2 expression in high dose Anchang Yuyang decoction group was significantly increased (P<0.01), and TLR4 expression was significantly decreased (P<0.01). Conclusions: Anchang Yuyang decoction can promote the repair of colonic mucosa in rats with ulcerative colitis, and its mechanism may be related to the increase of TFF3 and MUC2 gene expressions and down regulation of TLR4 gene expression.

Key wordsColitis, Ulcerative;Anchang Yuyang Decoction;Trefoil Factor 3;Mucin-2;

Toll-Like Receptor 4;Therapy

溃疡性结肠炎(UC)是一种主要累及直肠、结肠黏膜和黏膜下层的慢性非特异性炎症，其病因和发病机制目前尚未完全阐明。西医治疗UC以氨基水杨酸类、激素等药物为主，存在不良反应多、费用昂贵、易复发等缺点，中医药治疗UC已成为研究热点。本研究的前期研究[1-3]发现，中药安肠愈疡汤可通过下调促炎因子白细胞介素(IL)-1、IL-8、肿瘤坏死因子(TNF)-α水平以及上调抗炎因子IL-10、IL-13水平，从而起治疗UC的作用。在此基础上，本研究通过评估安肠愈疡汤对UC大鼠结肠组织中肠三叶因子(TFF3)、黏蛋白2(MUC2)和Toll样受体4(TLR4)基因表达的影响，旨在从基因水平上探讨安肠愈疡汤治疗UC的机制。……