中国药房2024，Vol.35Issue(1)：51-56,6.DOI:10.6039/j.issn.1001-0408.2024.01.09
柠檬苦素对溃疡性结肠炎大鼠肠道损伤和肠道菌群紊乱的改善作用及机制
Improvement effects of limonin on intestinal injury and intestinal flora disturbance in rats with ulcerative colitis and its mechanism
摘要
Abstract
OBJECTIVE To investigate the improvement effects of limonin on intestinal injury and intestinal flora disturbance in rats with ulcerative colitis(UC)and its mechanism.METHODS UC rat models were established,and 70 rats with successful modeling were randomly divided into model group,limonin low-,medium-,and high-dose groups(12.5,25,50 mg/kg),and sulfasalazine group(positive control group,500 mg/kg),with 14 rats in each group.Another 14 rats were selected as the control group.After modeling,each group was given the corresponding drug or equal amount of normal saline,once a day,for 2 weeks.Twenty-four hours after the last administration,the general condition of rats was observed and the body weight was measured,and colon tissue was collected for colonic mucosal damage index(CMDI)scoring;the levels of interleukin-1β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α)in colon tissue were detected;the pathological changes of colon tissue were observed;the protein expressions of Claudin-1,Occludin,ZO-1,high mobility group protein B1(HMGB1)and receptor for advanced glycation end products(RAGE)in colon tissue were detected;fecal 16S rRNA sequencing was used to detect the relative abundance of intestinal microbiota in rats.RESULTS Compared with the control group,the rats in the model group were in poor mental state,with darker fur,irritable mood,disordered arrangement of colon glands,inflammatory cell infiltration,cell necrosis and edema;CMDI score,the levels of IL-1β,IL-6 and TNF-α,protein expressions of HMGB1 and RAGE in colon tissue,the relative abundance of Proteobacteria and Bacteroidetes were significantly increased(P＜0.05);body weight,the protein expressions of Claudin-1,Occludin and ZO-1 in colon tissue,the relative abundance of Firmicutes in the intestine were significantly decreased(P＜0.05).Compared with the model group,general situation and pathological damage of colonic tissue in limonin groups were improved,the levels of the above indicators were significantly reversed(P＜0.05),and in a dose-dependent manner(P＜0.05);there was no significant difference in various indexes between sulfasalazine group and limonin high-dose group(P＞0.05).CONCLUSIONS Limonin can improve intestinal injury and intestinal flora disturbance in UC model rats,the mechanism of which may be associated with the down-regulation of HMGB1/RAGE signaling pathway.关键词
柠檬苦素/溃疡性结肠炎/肠道损伤/肠道菌群/高迁移率族蛋白B1/晚期糖基化终末产物受体信号通路Key words
limonin/ulcerative colitis/intestinal injury/intestinal flora/HMGB1/RAGE signaling pathway分类
医药卫生引用本文复制引用
张霞,贾慧宇,康金旺,赵汉清..柠檬苦素对溃疡性结肠炎大鼠肠道损伤和肠道菌群紊乱的改善作用及机制[J].中国药房,2024,35(1):51-56,6.基金项目
河北省医学科学研究课题计划项目(No.20210853) （No.20210853）
