健脾化湿方对右旋葡聚糖硫酸钠诱导的溃疡性结肠炎小鼠肠道菌群的影响  

Effects of Jianpi Huashi Formula on intestinal flora in mice with ulcerativecolitis induced by dextran sodium sulfate

作　　者：徐张扬 蒋蓓尔 张建 刘光盛 王杨凯 闵天骄 何颖 XU Zhangyang;JIANG Beier;ZHANG Jian;LIU Guangsheng;WANG Yangkai;MIN Tianjiao;HE Ying(Marine Biomedicine and Polar Medicine Laboratory,Naval Medical Center,Shanghai 200433,China;School of Basic Medicine,Naval Medical University,Shanghai 200433,China;Graduate School,Naval Medical University,Shanghai 200433,China)

机构地区：[1]海军特色医学中心海洋生物医药与极地医学研究室,上海200433 [2]海军军医大学基础医学院,上海200433 [3]海军军医大学研究生院,上海200433

出　　处：《药学研究》2023年第9期661-667,共7页Journal of Pharmaceutical Research

基　　金：海装军内科研重点项目(No.16A211);。

摘　　要：目的 研究健脾化湿方对右旋葡聚糖硫酸钠(DSS)诱导的溃疡性结肠炎(UC)的作用及作用机制。方法 将C57BL/6小鼠随机分为正常对照组、模型组、美沙拉嗪组及健脾化湿组。对照组给予正常饮用水,其他组均自由饮用3%DSS水溶液,连续饮用7 d,建立UC小鼠动物模型;造模第1天同步开始灌胃给药,连续给药9 d,每天记录小鼠体质量、大便性状及便血情况。药物干预治疗9 d后处死小鼠,测量结肠长度,取结肠进行HE染色进行病理组织学检查,ELISA法检测小鼠结肠组织中的肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-1β(IL-1β)水平,并通过16S rRNA测序检测小鼠肠道菌群的变化。结果 健脾化湿方给药后可有效缓解小鼠结肠炎症状,降低结肠组织中炎症因子TNF-α、IL-6和IL-1β的表达,对UC小鼠有较好的治疗效果;菌群测序结果显示,模型组小鼠与正常对照组相比,肠道菌群多样性降低,经健脾化湿方治疗后,与模型组相比,菌群多样性明显提高,在门水平上主要表现为厚壁菌门和变形菌门显著降低,拟杆菌门丰度增高,属水平上主要表现为Akkermansia增高和幽门螺杆菌降低。结论 健脾化湿方可能通过改善和恢复菌群多样性,调节UC小鼠菌群组成从而发挥治疗UC的作用。Objective To study the effect and mechanism of the Jianpi Huashi Formula(JHF)on ulcerative colitis(UC)induced by dextran sulfate sodium(DSS).Methods C57BL/6 mice were randomly divided into normal control group,model group,positive group(mesalazine group),and JHF groups.The control group was given normal drinking water,and the other groups were given 3%DSS water solution freely for 7 days to establish the animal model of UC mice.The mice were administrated by gavage from the first day of modeling for 9 consecutive days,and the body mass,stool properties,and blood in stool were recorded every day.The mice were sacrificed after 9 days of drug intervention.The length of the colon was measured.The colon was harvested for HE staining and histopathological scoring.ELISA was used to measure the levels of tumor necrosis factor-0x0E䥺SymbolaA@0x0F(TNF-0x0E䥺SymbolaA@0x0F),interleukin-6(IL-6),and interleukin-1β(IL-1β)in the colon tissue of mice.The changes in intestinal microbiota in mice were detected by 16S rRNA sequencing.Results The Jianpi Huashi Formula(JHF)can effectively alleviate the symptoms of colitis in mice and reduce the expression of inflammatory factors TNF-α,IL-6 and IL-1βin colon tissues,showing a better therapeutic effect on UC mice.The results of microbiota sequencing showed that the diversity of intestinal flora in the model group was reduced compared with the normal control group.After treatment with the JHF,the diversity of bacterial flora was significantly increased compared with the model group.At the phylum level,it mainly showed that the abundance of Firmicutes and Proteobacteria significantly decreased,while that of Bacteroidetes increased.At the genus level,it mainly showed that there was an increase in Akkermansia and a decrease in Helicobacter.Conclusion JHF may play a role in treating UC by improving and restoring the diversity of bacterial flora and regulating the composition of bacterial flora in UC mice.

关 键 词：健脾化湿方 溃疡性结肠炎 炎症因子 肠道菌群 

分 类 号：R285.5[医药卫生—中药学]