膳食纤维联合美沙拉嗪治疗溃疡性结肠炎的疗效与机制  

Effect and Mechanism of Dietary Fiber Combined with Mesalazine in the Treatment of Ulcerative Colitis

作　　者：于沛 何贺 钞艳惠 聂会娟[1] YU Pei;HE He;CHAO Yanhui;NIE Huijuan(Department of Pharmacy,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院药学部,郑州450052

出　　处：《医药导报》2021年第11期1487-1493,共7页Herald of Medicine

摘　　要：目的观察膳食纤维联合美沙拉嗪(5-ASA)治疗溃疡性结肠炎(UC)的疗效与机制。方法采用葡聚糖硫酸钠制备C57BL/6小鼠UC模型,将模型小鼠分为模型对照组、5-ASA组及膳食纤维联合5-ASA(F-5-ASA)组,设未造模小鼠为正常对照组。5-ASA组与F-5-ASA组灌胃5-ASA,200 mg·kg^(-1)·d^(-1),共7 d;F-5-ASA组给予膳食纤维饲料,其他3组给予正常饲料。记录小鼠体质量及疾病活动指数评分(DAI);实验结束测定小鼠结肠长度及结肠组织白细胞介素1β(IL-1β)、IL-6、肿瘤坏死因子α(TNF-α)与IL-10,观察结肠组织病理切片;16S RNA高通量测序分析小鼠肠道菌群。结果与模型对照组比较,5-ASA组与F-5-ASA组小鼠体质量明显上升(均P<0.01)、DAI评分降低(均P<0.01),结肠长度明显增加(均P<0.01)。病理切片显示,5-ASA组与F-5-ASA组小鼠结肠结构层次重构,黏膜重塑,隐窝少量炎性细胞浸润,F-5-ASA组疗效优于5-ASA组。与模型对照组比较,F-5-ASA组IL-1β、IL-6和TNF-α表达量显著下调,IL-10显著上调(均P<0.01)。16S RNA肠道菌群和代谢途径分析结果显示,F-5-ASA组小鼠肠道菌群多样性改善,包括Bacteroides、Parabacteroides、Campylobacter、Helicobacter和Eubacterium等在内的9种菌属丰度显著提高;碳水化合物代谢、酪氨酸与色氨酸生物合成、包括氨基酸代谢在内的22种代谢途径显著上调(P<0.05),包括丙酸代谢、细菌趋化性和细菌运动蛋白等在内的23种代谢途径显著上调(P<0.05)。结论膳食纤维联合5-ASA可通过调控肠道菌群治疗小鼠UC。Objective To study the effect and mechanism of dietary fiber combined with mesalazine in ulcerative colitis(UC).Methods A C57BL/6 mouse model of UC was established by using dextran sulfate sodium.The mice were randomly divided into four groups,including normal group(Control),model control group(Model),mesalazine group(5-ASA),and dietary fiber combined with mesalazine group(F-5-ASA).The 5-ASA and F-5-ASA groups were given 200 mg·kg^(-1) of 5-ASA for 7 days.The F-5-ASA group was given dietary fiber feed,whereas the normal,Model and 5-ASA groups were fed with normal feed.During the study,body mass and disease activity index(DAI)score were observed.At the end of experiment,the protein expression of interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α)and IL-10 were tested,the colon length was measured and histological pathology were observed.Intestinal flora abundance of 16S RNA was analyzed by next-generation sequencing analysis method.Results Compared with model control group,the body mass of mice in the 5-ASA group and F-5-ASA group was increased significantly(all P<0.01),the DAI score was decreased(all P<0.01)and the colon length increased significantly(all P<0.01).The pathological sections showed that the colon structure of the mice in the 5-ASA group and the F-5-ASA group was remodeled,mucous membrane was remodeled,and crypts had a small amount of inflammatory cell infiltration.In addition,F-5-ASA had better efficacy than the 5-ASA.The results showed the expression of IL-1β(P<0.01),IL-6 and TNF-α(P<0.01)(P<0.01)in the F-5-ASA group was significantly down-regulated,and IL-10 was significantly increased(P<0.01)when compared with model control group.The 16S RNA intestinal flora and metabolic pathway analysis showed that the diversity of the intestinal flora of mice in the F-5-ASA group was improved.And the abundance of species,such as Bacteroides,Parabacteroides,Campylobacter,Helicobacter and Eubacterium,was significantly increased.At the same time,22 metabolic pathways were significantly up-regulated(P

关 键 词：美沙拉嗪 膳食纤维 溃疡性结肠炎 肠道菌群 

分 类 号：R975[医药卫生—药品] R965[医药卫生—药学]