复方芩柏颗粒对溃疡性结肠炎大鼠肠道菌群的调控及对肠道黏膜病理的影响

作者：刚 鑫，罗雯鹏，潘 燎，王真权

单位：湖南中医药大学第二附属医院，湖南 长沙 410000

引用：引用：刚鑫，罗雯鹏，潘燎，王真权.复方芩柏颗粒对溃疡性结肠炎大鼠肠道菌群的调控及对肠道黏膜病理的影响[J].中医药导报,2025,31(1):53-60.

DOI：10.13862/j.cn43-1446/r.2025.01.010

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摘要：

目的：探究复方芩柏颗粒对葡聚糖硫酸钠（DSS）诱导的溃疡性结肠炎（UC）模型大鼠肠道菌群的影响。方法：将42只健康SD雄性大鼠随机分为正常组12只和模型制备组30只，采用DSS构建大鼠UC模型，每组各取3只确定是否造模成功，将造模成功大鼠随机分为模型组（UC）、美沙拉嗪组（ME）与复方芩柏颗粒组（QB）各9只，观察各组大鼠一般情况，记录疾病活动指数（DAI）评分，进行HE染色后观察肠道病理变化，运用酶联免疫吸附试验（ELISA）法检测大鼠血清炎症因子水平，高通量测序技术检测肠道菌群物种组成及丰度的变化，进行物种多样性分析。结果：模型组大鼠DAI评分高于正常组（P<0.01），模型组大鼠结肠黏膜损伤严重，模型组白介素-6（IL-6）、白介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）水平显著升高，白介素-10（IL-10）水平较正常组显著降低（P<0.01）；与模型组比较，复方芩柏颗粒组大鼠DAI评分下降（P<0.01），结肠黏膜损伤及淋巴细胞浸润减轻，IL-6、IL-1β、TNF-α水平显著降低，IL-10水平显著升高（P<0.05）。16S rDNA基因测序结果提示DSS诱导UC后小鼠肠道菌群多样性降低，给药后UC大鼠肠道菌群多样性升高。复方芩柏颗粒组Shannon指数及Simpson指数较模型组明显升高，Chao1指数较模型组下降（P<0.05）；复方芩柏颗粒组变形杆菌门、拟杆菌门相对丰度较模型组显著下降，厚壁菌门及放线菌门相对丰度较模型组显著上调（P<0.05），复方芩柏颗粒组双歧杆菌属、唾液联合乳杆菌属、嗜黏蛋白-阿克曼氏菌属、杜氏杆菌属、理研菌属相对丰度较模型组显著上调，梭杆菌属、大肠埃希·志贺菌属、普拉梭菌、链球菌属、罗氏菌属、毛螺菌属的相对丰度下降（P<0.05）；LEfSe分析示复方芩柏颗粒组杆菌纲、乳酸杆菌属的相对丰度有升高趋势；PICRUSt2功能预测示复方芩柏颗粒组在氨基糖和核苷酸糖代谢、谷胱甘肽代谢、亚酸油代谢、果糖和甘露糖代谢等功能通路上的相对丰度有上调趋势。结论：复方芩柏颗粒可通过调节肠道菌群的丰度和多样性、恢复菌群结构来影响肠道菌群，从而修复损伤的肠黏膜屏障。

关键词：溃疡性结肠炎；复方芩柏颗粒；肠道菌群；16S rDNA基因测序；大鼠

Abstract：Objective: To explore the effects of compound Qinbai granule on the intestinal flora of rats with ulcerative colitis (UC) induced by sodium dextran sulfate (DSS). Methods: Totally 42 healthy SD male rats were randomly divided into normal group (n=12) and model preparation group (n=30). UC model was established by DSS, and 3 rats were selected from each group to determine whether the modeling was successful. The successful model rats were randomly divided into model group (UC), mesalazine group (ME) and compound Qinbai granules group (QB), with 9 rats in each group. The general situation of rats was observed, and score the disease activity index (DAI) was recorded. The intestinal pathological changes under the biological microscope were observed after Hematoxylin-eosin (HE) staining. Enzyme linked immunosorbent assay (ELISA) method was used to detect levels of serum inflammatory factor, and high-throughput sequencing technology was used to detect the changes in the composition and abundance of intestinal flora species. Results: The model group showed higher DAI scores than normal group (P<0.01), and the pathological section showed that the colonic mucosa of rats was seriously damaged in model group. Compared with the normal group, the serum levels of IL-6, IL-1β and TNF-α increased in model group, while the level of IL-10 decreased in model group (P<0.01). Compared with the model group, the DAI scores decreased in compound Qinbai granules group (P<0.01), and the colon injury was alleviated in compound Qinbai granules group. The levels of IL-6, IL-1β and TNF-α decreased in compound Qinbai granules group, while level of IL-10 increased in compound Qinbai granules group (P<0.05). The sequencing of 16S rRNA gene showed a decreased diversity of intestinal flora in rats with UC induced by DSS, and the diversity of intestinal flora in UC rats increased after administration. The compound Qinbai granules group showed higher Shannon index and Simpson index than model group, while lower Chao1 index than model group (P<0.05). The compound Qinbai granules group showed lower relative abundance of Proteobacteria and Bacteroidetes than model group, while higjer relative abundance of Firmicutes and Actinobacteria than model group (P<0.05). The abundance of Bifidobacterium, Salivary Lactobacillus, Mucinophilus Ackermann, Duraliella, and Physiobacteria in compound Qinbai granules group was significantly upregulated compared to the model group, while the relative abundance of Fusobacterium, Escherichia coli Shigella, Plasmobacter, Streptococcus, Rochella, and Trichospira decreased in compound Qinbai granules group (P<0.05). LefSe analysis showed an increasing trend in the relative abundance of Bacteroids and Lactobacillus genera in compound Qinbai granules group. PICRUSt2 functional prediction showed an upward trend in the relative abundance of the compound Qinbai granules group in functional pathways such as amino and nucleotide sugar metabolism, glutathione metabolism, linoleic acid oil metabolism, fructose and mannose metabolism. Conclusion: Compound Qinbai granules can affect the interacting flora by regulating its abundance and diversity, and restoring its structure, and then repair the damaged intestinal mucosal barrier.

Key words：ulcerative colitis; compound Qinbai granules; intestinal flora; 16S rDNA gene sequencing; rat

发布时间：2025-11-28

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