黄连素调控肠道菌群缓解诱导性小鼠结肠炎

Berberine Ameliorates DSS-Induced Colitis via Regulating Intestinal Microbiota

目的探讨黄连素对葡聚糖硫酸钠(DSS)诱导性小鼠结肠炎和肠道菌群的影响。方法40只雄性C57BL/6小鼠按照随机数字表法分为4组即空白对照组(正常喂养,无菌水灌胃)、黄连素组(正常喂养,黄连素灌胃)、模型组(3%DSS喂养,无菌水灌胃)、黄连素治疗组(3%DSS喂养,黄连素灌胃);测量并记录4组体重和疾病活动指数(DAI);采用苏木精伊红(HE)染色观察结肠组织病理改变;利用16S核糖体RNA(rRNA)分析黄连素对肠道菌群的影响。结果与空白对照组比较,模型组小鼠体重显著降低(P<0.001),DAI显著增加(P<0.001)。与模型组比较,黄连素治疗组小鼠的体重减轻显著缓解(P<0.001),DAI评分显著降低(P<0.001)。HE结果显示,空白对照组和黄连素组小鼠的肠壁结构完整,而模型组小鼠结肠组织结构紊乱,腺体消失,可见大量炎症细胞浸润;与模型组比较,黄连素治疗组小鼠结肠黏膜肌层及肠腺排列较为完整,炎症细胞浸润较少,组织学评分显著降低(P<0.05)。rRNA分析结果显示,与空白对照组比较,模型组小鼠肠道菌群的α多样性显著降低(P<0.01),志贺杆菌和肠球菌的丰度显著增加(P<0.01)。与模型组比较,黄连素治疗组小鼠肠道菌群的α多样性显著增加(P<0.01),志贺杆菌和肠球菌的丰度显著降低(P<0.05)。结论黄连素可有效缓解DSS诱导的小鼠结肠炎。DSS诱导性结肠炎小鼠肠道菌群紊乱,黄连素治疗后可以恢复结肠炎小鼠肠道菌群的生物多样性,同时降低致病性志贺杆菌和肠球菌的丰度。

Objective To investigate the effects of berberine on colitis induced by dextran sulfate sodium(DSS)and intestinal flora in mice.Methods Forty male C57BL/6 mice were randomly divided into four groups:control group(mice received normal diet and intragastrical administration of sterile water),berberine group(mice received normal diet and intragastrical administration of berberine),DSS group(mice received DSS and intragastrical administration of sterile water),and berberine-treated DSS group(mice received 3%DDS and intragastrical administration of berberine).The body weight and disease activity index(DAI)were recorded daily.The histopathological changes in colon were observed by Hematoxylin/Eosin(HE)staining.The 16S rRNA analysis was used to reveal the effect of berberine on intestinal flora.Results Compared with the control group,body weight decreased and DAI increased in the DSS group(P<0.001).However,berberine treatment alleviated DSS-induced reduction in body weight and increase in DAI(P<0.001).HE staining showed intact intestinal wall structure in the control group and berberine group.In the DSS group,colon tissue displayed structure disorganization,gland disappearance and widespread inflammatory cell infiltration.Compared with the DSS group,the arrangement of colonic mucosa and intestinal glands was relatively complete with less inflammatory cell infiltration and reduced histological score in berberine-treated DSS group(P<0.05).Compared with the control group,theα-diversity of intestinal flora decreased and the abundance of Escherichia shigella and Enterococcus increased in the DSS group(P<0.01).Nevertheless,compared with the DSS group,theα-diversity of intestinal flora increased and the abundance of Escherichia shigella and Enterococcus decreased in the berberine-treated DSS group(P<0.05).Conclusion DSS-induced colitis is associated with intestinal flora disorder,and can be effectively relieved by berberine in mice.Furthermore,berberine treatment can restore the biodiversity of intestinal flora and reduce the abundance of Escherichia shigella and Enterococcus in mice with colitis.