三点金中黄酮类化合物对溃疡性结肠炎小鼠的干预作用及其对肠道菌群的影响

Therapeutic effect of flavonoids from Desmodium triflorum on an ulcerative colitis mouse model and the influence on intestinal flora

目的探讨民族药三点金总黄酮及其中单体化合物毛蕊异黄酮和刺芒柄花素对右旋葡聚糖硫酸钠(DSS)诱导的溃疡性结肠炎(UC)小鼠的干预作用及对其肠道菌群的影响。方法用3%DSS构建UC小鼠模型,将30只C57BL/6小鼠分为正常组、模型组、三点金总黄酮组(500 mg/kg)、毛蕊异黄酮组(100 mg/kg)以及刺芒柄花素组(100 mg/kg)。观察小鼠体重变化,进行疾病活动指数(DAI)、结肠组织病理学评分,检测小鼠血清中IL-1β和IL-6含量,通过高通量测序分析小鼠肠道菌群的变化。结果三点金总黄酮、毛蕊异黄酮以及刺芒柄花素可有效减轻小鼠结肠炎症状,降低炎症因子表达;菌群测序结果显示三点金总黄酮、毛蕊异黄酮以及刺芒柄花素使得肠道菌群的多样性明显提高,科水平上主要表现为致病菌群螺杆菌科比例降低,Muribaculaceae和毛螺菌科比例升高;属水平上主要表现为乳酸菌属的增加和条件致病菌拟杆菌的减少;种水平上主要表现对机会致病菌拟杆菌和大肠杆菌的减少。结论三点金总黄酮、毛蕊异黄酮以及刺芒柄花素对UC小鼠的体征及炎性因子有一定的改善作用,对肠道菌群有良好的恢复作用。

Objective The purpose of this study was to investigate the effect of total flavones of Desmodium triflorum,calycosin and formononetin from D.triflorum on mice with dextran sodium sulfate(DSS)-induced ulcerative colitis(UC)and analyze the effects on intestinal flora.Methods Thirty C57BL/6 mice were treated with 3%DSS to establish the UC model and divided into the normal group,model group,total flavones of Desmodium triflorum group(500 mg/kg),calycosin group(100 mg/kg)and formononetin group(100 mg/kg).Body weight changes,disease activity index(DAI),colon histopathology score and IL-1βand IL-6 cytokine expression levels in the serum of the mice were determined,and changes of intestinal flora in mice were detected by high-throughput sequencing.Results Administration of total flavones of D.triflorum,calycosin and formononetin from D.triflorum effectively alleviated colonic inflammatory symptoms and reduced the expression of inflammatory factors in UC mice,Resulting in a good therapeutic effect.Treatment with total flavones of D.triflorum,calycosin and formononetin from D.triflorum significantly increased the diversity of intestinal microflora.The proportion of Helicobacteraceae was decreased and those of Muribaculaceae and Lachnospiraceae were increased at the family level.The proportion of Bacteroides was decreased and that of Lactobacillus was increased at the genus level.Regarding the species level,the proportions of Bacteroides and Escherichia coli were decreased.Conclusions Total flavones of D.triflorum,calycosin and formononetin from D.triflorum improve the changes of physical signs and inflammatory factors of UC mice and had a good recovery effect on intestinal flora.