山西医科大学学报2025，Vol.56Issue(11)：1242-1251,10.DOI:10.13753/j.issn.1007-6611.2025.11.006
基于肠道菌群/LPS轴探讨甘草酚对结肠损伤小鼠的保护作用
Protective effect of glycyrol against colonic injury in mice via gut microbiota/LPS axis
摘要
Abstract
Objective To investigate whether glycyrol(GC)alleviates 5-fluorouracil(5-FU)-induced intestinal injury in mice by modulating the gut microbiota and the cellular autophagy.Methods Thirty-two 5-week-old male SPF-grade BALB/c mice(approxi-mately 18 g)were randomly divided into four groups:control group,glycyrol(GC)group,model group(5-FU-induced colon injury),and glycyrol+5-FU group.The mice in control group received daily intragastric administration of normal saline at days 1-14 and daily intraperitoneal injection of normal saline at days 12-14.The mice in GC group received daily intragastric administration of glycyrol(20 mg/kg)at days 1-14 and daily intraperitoneal injection of normal saline from days 12-14.The mice in model group received daily intragastric administration of normal saline at days 1-14 and daily intraperitoneal injection of 5-FU(100 mg/kg)at days 12-14.The mice in glycyrol+5-FU group received daily intragastric administration of glycyrol(20 mg/kg)at days 1-14 and daily intraperitoneal injection of 5-FU(100 mg/kg)at days 12-14.Body weight and food intake were measured daily.On the final day of the experiment,fecal samples were collected for 16S rRNA sequencing to analyze the gut microbiota structure and function.After euthanasia,the thymus and the spleen were harvested to calculate thymus index and spleen index.Serum lipopolysaccharide(LPS)and colon tumor necrosis factor-α(TNF-α)concentrations were detected by enzyme-linked immunosorbent assay(ELISA).Colon histopathological changes were observed by HE staining.The expressions of autophagy-related proteins p62 and LC3-Ⅱ in colon tissue were detected by Western blot.The human colon cancer cell line HCT116 was divided into normal control group,GC group(cultured with 20 μmol/L GC for 48 h),LPS group(cultured with 1 μg/L LPS for 48 h),and GC+LPS group(cultured with 20 μmol/L GC and 1 μg/L LPS for 48 h).The levels of autophagy-related proteins LC3-Ⅱ and p62 in HCT116 cells were detected by Western blot.Results Compared with control group,no significant differences were observed in any indicators at day 14 in GC group.Compared with control group,body weight and food intake significantly decreased in model group(P<0.01),thymus index and spleen index were significantly reduced(P<0.01),significant inflammatory cell infiltration in colon tissue was found by HE staining,colon TNF-α concentration was significantly in-creased(P<0.01),serum LPS was significantly elevated(P<0.05),the relative abundances of LPS-producing bacteria including Bacteroides,Helicobacter,and Lachnospiraceae,were significantly increased(P<0.05),p62 expression in colon tissue was signifi-cantly increased(P<0.05),and LC3-Ⅱ expression was significantly decreased(P<0.01).Compared with model group,body weight,food intake,thymus index,and spleen index were significantly increased in glycyrol+5-FU group(P<0.05);the pathological damage in colon tissue was alleviated by HE staining;TNF-α and LPS concentrations were significantly decreased(P<0.05);the relative abundances of LPS-producing bacteria Bacteroides,Helicobacter,and Lachnospiraceae were significantly reduced(P<0.05);p62 expression in colon tissue significantly decreased(P<0.05),and LC3-Ⅱ was significantly increased(P<0.05).In HCT116 cells,compared with control group,the levels of autophagy-related proteins p62 and LC3-Ⅱ showed no significant differences in GC group.Compared with control group,p62 level was significantly increased in LPS group(P<0.01),and LC3-Ⅱ level was significantly decreased(P<0.01).Compared with LPS group,p62 level was decreased while LC3-Ⅱ level was increased in GC+LPS group(P<0.05).Conclusion Glycyrol may protect the intestine by modulating the gut microbiota,inhibiting the excessive LPS production,and restoring the autophagy levels.关键词
甘草酚/结肠损伤/肠黏膜屏障/肠道菌群/脂多糖/自噬Key words
glycyrol/colon injury/intestinal mucosal barrier/gut microbiota/LPS/autophygy分类
医药卫生引用本文复制引用
XU Jiali,SU Yuting,LU Shangyun,ZHANG Chang,WANG Xiaocheng..基于肠道菌群/LPS轴探讨甘草酚对结肠损伤小鼠的保护作用[J].山西医科大学学报,2025,56(11):1242-1251,10.基金项目
国家自然科学基金青年科学基金项目(82304147) （82304147）
空军军医大学航空航天医学系文职人员成长扶持"引航计划"项目(2024HYYH07) （2024HYYH07）
