鱼腥草多糖对DSS诱导小鼠结肠炎的改善作用

吴苹; 刘晋倩; 董晶; 王硕; 范宗强; 李震; 王帅珂; 陈芳

doi:10.13386/j.issn1002-0306.2021030063

鱼腥草多糖对DSS诱导小鼠结肠炎的改善作用

Improving Effect of Houttuynia Cordata Polysaccharide on Dextran Sodium Sulfate-induced Ulcerative Colitis

摘要

摘要: 目的： 探究鱼腥草多糖（Houttuynia cordata polysaccharides，HCP）对葡聚糖硫酸钠诱导的溃疡性结肠炎的疗效及可能的作用机制。 方法： 将雄性昆明小鼠随机分为5组（n=10），分别为空白组、模型组、鱼腥草低剂量组、鱼腥草高剂量组和柳氮磺胺吡啶（SASP）阳性药物对照组。采用2.5%葡聚糖硫酸钠（Dextran sulfate sodium salt，DSS）水溶液让小鼠自由饮用9 d，诱导溃疡性结肠炎(Ulcerative colitis，UC)模型。建模成功后，空白组和模型组自由饮用蒸馏水，鱼腥草多糖低、高剂量组分别灌胃1、2 g/kg/d鱼腥草多糖溶液，阳性药物组灌胃柳氮磺胺吡啶9 mg/kg/d，连续干预6 d。评估疾病活动指数（Disease activity index，DAI），HE染色观察结肠组织病理切片，ELISA 检测血清中炎症细胞因子肿瘤坏死因子-α（TNF-α）、γ-干扰素（IFN-γ）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）水平以及肝肾功能指标谷丙转氨酶（ALT）、谷草转氨酶（AST）、肌酐（CR）、尿素氮（BUN）含量，16S rRNA系统测序技术检测分析小鼠肠道菌群的变化，研究鱼腥草多糖对小鼠结肠炎的影响。 结果： 与模型组相比，鱼腥草多糖组能够显著的降低DAI评分(P<0.05)，减少结肠组织溃疡面积，显著性降低TNF-α、IL-1β、IL-6、IFN-γ的水平(P<0.01)和ALT、AST、CR、BUN的含量(P<0.05，P<0.01)，增加肠道菌群的丰富度。 结论： 鱼腥草多糖可缓解溃疡性结肠炎小鼠的症状，其作用效果可能与改善肠道黏膜环境、降低炎症因子水平和维持肠道菌群的稳态有关。

Abstract: Objective : To explore the effect of Houttuynia cordata polysaccharide (HCP) on dextran sulfate sodium salt (DSS) induced ulcerative colitis (UC) and its possible mechanism in mice. Methods : Fifty KM male mice were randomly divided into 5 groups (n=10): normal control group, model group, HCP low dose group (1 g/kg/day), HCP high dose group (2 g/kg/day), and Sulfasalazine positive group (SASP, 9 mg/kg/d). The UC model was induced with 2.5% DSS by water drinking for 9 days in mice. After successfully established the model in mice, the normal control group and the model group were free drinking distilled water, HCP in doses of 1 g/kg/day and 2 g/kg/day groups were given by filling to the stomach after DSS administration, and the positive group was treated with 9 mg/kg/d Sulfasalazine aqueous solution for 6 days. Assessing disease activity index (DAI) of mice in each group, observing colonic tissue structure by HE, detecting pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), leukocyte-mediated interleukin-1β (IL-1β) and interleukin-6 (IL-6) contents and detecting the liver and kidney biochemical indexs levels alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CR) and blood urea nitrogen (BUN) in serum by ELISA method, using 16S rRNA phylogenetic sequencing to detect the changes of intestinal flora in rat feces. Results : Compared with the model group, the DAI scores in both dosages of HCP were significantly decreased (P<0.05), the colonic tissue structures were dose-dependently improved. Also, HCP dose-dependently decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IFN-γ) and the contents of liver and kidney biochemical indexs (ALT, AST, CR, BUN). In addition, the gut microbiota imbalance was modulated in HCP treated groups during colitis by increasing the gut microbial diversity. Conclusion : HCP may alleviate the symptoms of ulcerative colitis by improving the intestinal mucosal environment, reducing the level of inflammatory factors and maintaining the homeostasis of intestinal flora in mice.