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胡锦洋,蒋士生,牛俊杰.芪连结肠宁对溃疡性结肠炎模型大鼠TLR4/NF-κB信号通路及肠道菌群的影响[J].湖南中医药大学学报英文版,2022,42(9):1442-1450.[Click to copy
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| 芪连结肠宁对溃疡性结肠炎模型大鼠TLR4/NF-κB信号通路及肠道菌群的影响 |
| 胡锦洋,蒋士生,牛俊杰 |
| (湖南省中西医结合医院, 湖南 长沙 410006) |
| 摘要: |
| 目的 基于肠道菌群及TLR4/NF-κB通路探讨芪连结肠宁治疗溃疡性结肠炎的可能作用机制。方法 健康雄性2个月龄SD大鼠40只，随机分为正常组、模型组、芪连结肠宁低剂量组、芪连结肠宁中剂量组及芪连结肠宁高剂量组，每组8只。采用5%葡聚糖硫酸钠喂养建立溃疡性结肠炎大鼠模型，连续治疗3周后检测指标。给药前后进行疾病活动指数（disease activity index,DAI）评分，HE染色观察结肠组织病理情况，免疫组织化学法观察结肠组织核因子κB（nuclear factor-κB,NF-κB）p65、Toll样受体4（Toll-like receptor 4,TLR4）蛋白表达情况，ELISA法测定血清中TLR4、NF-κB p65、白介素-6（interleukin-6,IL-6）、肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）蛋白含量，实时荧光定量PCR检测结肠组织TLR4、NF-κB p65、IL-6、TNF-α mRNA的表达，16S rRNA检测大鼠粪便中肠道菌群的多样性及分布情况。结果 与正常组比较，模型组大鼠肠道出现明显的病理损伤，DAI评分明显升高（P＜0.01），血清及结肠组织中TNF-α、IL-6、TLR4、NF-κB p65蛋白含量及mRNA表达均明显增加（P＜0.01），肠道菌群多样性及丰度均明显降低（P＜0.05，P＜0.01），Bacteroidota、Campilobacterota菌门和Prevotella菌属均明显增加（P＜0.05，P＜0.01），Firmicutes、Spirochaetota菌门和norank_f_Muribaculaceae、Lactobacillus菌属均明显减少（P＜0.01）。与模型组比较，芪连结肠宁各剂量组大鼠肠道病理损伤不同程度减轻，DAI评分均明显降低（P＜0.05，P＜0.01），血清及结肠组织中TNF-α、IL-6、TLR4、NF-κB p65蛋白含量及mRNA表达均明显降低（P＜0.05，P＜0.01），芪连结肠宁中剂量组肠道菌群多样性及丰度均明显增加（P＜0.05，P＜0.01）。结论 芪连结肠宁可有效缓解溃疡性结肠炎模型大鼠结肠组织病理损伤，增加肠道菌群多样性及丰富度，调控肠道菌群物种分布，介导TLR4/NF-κB信号通路，减轻炎症反应。 |
| 关键词: 溃疡性结肠炎 芪连结肠宁 肠道菌群 炎症 Toll样受体4 核因子κB |
| DOI：10.3969/j.issn.1674-070X.2022.09.005 |
| Received:July 07, 2022 |
| 基金项目:湖南省中医药科研计划青年课题(2021177);湖南省中医药研究院联合基金重点项目(202118);湖南省中医药研究院青年基金项目(201922);全国名老中医药专家蒋士生传承工作室建设项目(国中医药人教函[2012]149)。 |
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| Effects of Qilian Jiechang Ning on TLR4/NF-κB signaling pathway and intestinal flora in ulcerative colitis model of rats |
| HU Jinyang,JIANG Shisheng,NIU Junjie |
| (Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan 410006, China) |
| Abstract: |
| Objective To explore the possible mechanism of Qilian Jiechang Ning in the treatment of ulcerative colitis based on intestinal flora and TLR4/NF-κB pathway. Methods Forty healthy male 2-month-old SD rats were randomly divided into a normal group, a model group, a low-dose Qilian Jiechang Ning group, a middle-dose Qilian Jiechang Ning group, and a high-dose Qilian Jiechang Ning group, with 8 rats in each group. A rat model of ulcerative colitis was established by feeding with 5% dextran sodium sulfate, and the indexes were detected after continuous treatment for 3 weeks. Disease activity index (DAI) score was performed before and after administration; HE staining was used to observe the pathological condition of colon; immunohistochemistry was used to observe nuclear factor-κB (NF-κB) p65 and Toll-like receptor 4 (TLR4) in colon tissue protein expression; TLR4, NF-κB p65, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) protein content in serum were determined by ELISA; TLR4, NF-κB p65, IL-6, TNF-α mRNA expression levels of colon tissue were detected by real-time fluorescence quantitative PCR; 16S rRNA was used to detect the diversity and distribution of intestinal flora in rat feces. Results Compared with the normal group, the rats in the model group had obvious pathological damage to the intestine; the DAI score was significantly increased (P<0.01); the protein and mRNA expression levels of TNF-α, IL-6, TLR4, NF-κB p65 in serum and colon tissue were increased (P<0.01); the diversity and abundance of intestinal flora were significantly decreased (P<0.05, P<0.01); Bacteroidota, Campilobacterota and Prevotella were significantly increased (P<0.05, P<0.01); Firmicutes, Spirochaetota, norank_f_Muribaculaceae and Lactobacillus were significantly decreased (P<0.01). Compared with the model group, the intestinal pathological damage of the rats in each dose group of Qilian Jiechang Ning was alleviated to different degrees, and the DAI score was significantly decreased (P＜0.05, P＜0.01). The protein content and mRNA expression of TLR4, IL-6, TLR4, NF-κB p65 in serum and colon tissues were decreased (P<0.05, P<0.01); the diversity and abundance of intestinal flora in the middle-dose Qilian Jiechang Ning group were increased (P<0.05, P<0.01). Conclusion Qilian Jiechang Ning can effectively alleviate the pathological damage of colon tissue in ulcerative colitis model rats, increase the diversity and abundance of intestinal flora, regulate the distribution of intestinal flora species, and mediate TLR4/NF-κB signaling pathway to reduce inflammatory response. |
| Key words: ulcerative colitis Qilian Jiechang Ning intestinal flora inflammation Toll-like receptor 4 nuclear factor-κB |
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