五味苦参肠溶胶囊对溃疡性结肠炎大鼠肠道菌群的影响

Effect of five-flavor Sophora falvescens enteric-coated capsules on intestinal flora in rats with ulcerative colitis

目的探讨五味苦参肠溶胶囊对溃疡性结肠炎(UC)大鼠肠道菌群的影响,为五味苦参肠溶胶囊治疗UC的作用机制研究提供参考。方法40只SPF级Wistar大鼠随机分为对照组、模型组、美沙拉嗪组和五味苦参肠溶胶囊组,除对照组外,其他3组饮用3%葡聚糖硫酸钠7 d建立UC模型。造模成功后,对照组、模型组大鼠予2 mL/kg体重0.9%氯化钠溶液灌胃,美沙拉嗪组大鼠予2 mL/kg体重美沙拉嗪悬浊液(0.2 g/kg)灌胃,五味苦参肠溶胶囊组大鼠予2 mL/kg体重五味苦参肠溶胶囊药物颗粒悬浊液(2.16 g/kg)灌胃,连续2周。取大鼠结肠组织,采用苏木精-伊红染色观察大鼠结肠组织病理学改变;收集大鼠粪便,对肠道菌群进行16S rDNA高通量测序和生物学信息分析,比较各组大鼠肠道菌群α和β多样性,采用LEfSe分析法筛选各组优势菌群。结果与对照组比较,模型组大鼠结肠组织隐窝大量缺失,大量炎性细胞浸润;与模型组比较,美沙拉嗪组、五味苦参肠溶胶囊组大鼠结肠组织隐窝少量缺失,少量或无炎性细胞浸润,组织损伤改善。α多样性分析结果显示,与对照组比较,模型组Chao1、Shannon指数升高,Simpson指数降低;与模型组比较,美沙拉嗪组、五味参苦参肠溶胶囊组Chao1、Shannon指数降低,Simpson指数升高(均P<0.05)。β多样性分析结果显示,五味苦参肠溶胶囊组与对照组样本距离小于模型组与对照组样本距离。LEfSe分析结果显示,模型组优势菌群主要为另枝菌属、颤螺菌属;五味苦参肠溶胶囊组优势菌群为瘤胃球菌属、普雷沃菌属。结论五味苦参肠溶胶囊可改善肠道菌群结构,增加瘤胃球菌属、普雷沃菌属等有益菌丰度,降低另枝菌属等致病菌丰度,缓解UC大鼠的炎症反应。

Objective To explore the impact of five-flavor Sophora flavescens enteric-coated capsules(FSEC)on the intestinal flora of rats with ulcerative colitis(UC),so as to provide the reference for the mechanism of FSEC in treating UC.Methods Forty SPF-grade Wistar rats were randomly divided into the control group,the model group,the mesalazine group and the FSEC group.Except the control group(0.9%sodium chloride solution),the other 3 groups used 3%dextran sulfate sodium(DSS)for 7 days to establish UC model.After successful modeling,the control group and the model group were given 2 mL/kgbw of 0.9%sodium chloride solution by gavage for 2 weeks,while the mesalazine group and the FSEC group were given 2 mL/kgbw of mesalazine suspension(0.2 g/kg)and FSEC granule suspension(2.16 g/kg),respectively.Pathological changes of colon tissue were observed after hematoxylin-eosin(HE)staining.Rat fecal samples were collected,and 16S rDNA high-throughput sequencing and bioinformatics analysis were performed on intestinal flora.Theαandβdiversity of intestinal flora among the four groups were compared,and the dominant flora was screened using LEfSe analysis.Results Compared with the control group,the model group showed a significant loss of colonic crypts and a large infiltration of inflammatory cells.Compared with the model group,the mesalazine group and the FSEC group exhibited a slight loss of colonic crypts,a small amount or an absence inflammatory cell infiltration,and improved tissue damage.Theα-diversity analysis showed that compared with the control group,the Chao1 and Shannon indices in the model group increased,while the Simpson index decreased;compared with the model group,the Chao1 and Shannon indices in the mesalazine group and the FSEC group decreased,and the Simpson index increased(all P<0.05).Theβ-diversity analysis showed that the sample distance between the FSEC group and the control group were more closer than that between the model group and the control group.LEfSe analysis results showed that the dominant bacteria in the model group were mainly from the Alistipes and Oscillospira.In the FSEC group,the dominant bacteria were from the Ruminococcus and Prevotella.Conclusion FSEC can improve the structures of intestinal flora,increase the abundance of beneficial bacteria such as Ruminococcus and Prevotella,reduce the abundance of pathogenic bacteria such as Alistipes,and alleviate the inflammatory response in UC rats.