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单月桂酸甘油酯通过抑制Th17、中性粒细胞、巨噬细胞的浸润及改变肠道微生物群来改善右旋糖酐硫酸钠诱导的急性结肠炎。

Glycerol monolaurate ameliorates DSS-induced acute colitis by inhibiting infiltration of Th17, neutrophils, macrophages and altering the gut microbiota.

作者信息

He Ke-Jie, Dong Jia-Hui, Ouyang Xiao-Mei, Huo Ya-Ni, Cheng Xiao-Shen, Lin Ying, Li Yue, Gong Guoyu, Liu Jingjing, Ren Jian-Lin, Guleng Bayasi

机构信息

Department of Gastroenterology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

Binhai County People's Hospital, Yancheng, China.

出版信息

Front Nutr. 2022 Aug 12;9:911315. doi: 10.3389/fnut.2022.911315. eCollection 2022.

DOI:10.3389/fnut.2022.911315
PMID:36034889
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9413164/
Abstract

BACKGROUND AND AIMS

Inflammatory bowel disease (IBD) places a heavy medical burden on countries and families due to repeated and prolonged attacks, and the incidence and prevalence of IBD are increasing worldwide. Therefore, finding an effective treatment is a matter of great urgency. Glycerol monolaurate (GML), which has a twelve-carbon chain, is a compound naturally found in human breast milk. Some studies have shown that GML has antibacterial and anti-inflammatory effects. However, the specific mechanism of action remains unclear.

METHODS

Acute colitis was established in mice using 3% DSS, and glycerol monolaurate (500 mg·kg-) was administered for two weeks. QPCR and western blotting were performed to examine the inflammatory status. Mice described were subjected to flow cytometry analysis for immune cell activation.

RESULTS

GML treated alleviated macroscopic symptoms such as shortened colons, increased spleen weight, and caused weight loss in mice with DSS-induced colitis. In addition, GML decreased the expression of pro-inflammatory factors (NF-α, IL-1β and IL-1α) and increased the expression of anti-inflammatory factors (IL-10 and TGF-β). GML inhibited the activation of the MAPK and NF-κB signalling pathways, improved tissue damage, and increased the expression of intestinal tight junction proteins. In addition, LPMCs extracted from intestinal tissue via flow cytometry showed that GML treatment led to a decrease of Th17 cells, Neutrophils and Macrophages. 16S rDNA sequencing showed that GML increased the abundance of commensal bacterium such as Akkermansia and Lactobacillus murinus.

CONCLUSIONS

We showed that oral administration of GML ameliorated DSS-induced colitis by inhibiting infiltration of Th17 cells, Neutrophils, and Macrophages, protecting the intestinal mucosal barrier and altered the abundance of commensal bacterium. This study provides new insights into the biological function and therapeutic potential of GML in the treatment of IBD.

摘要

背景与目的

炎症性肠病(IBD)因反复发作且病程迁延,给国家和家庭带来沉重的医疗负担,且IBD在全球的发病率和患病率都在上升。因此,找到有效的治疗方法迫在眉睫。单月桂酸甘油酯(GML)有一条十二碳链,是一种天然存在于人乳中的化合物。一些研究表明GML具有抗菌和抗炎作用。然而,其具体作用机制仍不清楚。

方法

用3%葡聚糖硫酸钠(DSS)在小鼠中建立急性结肠炎模型,并给予单月桂酸甘油酯(500 mg·kg-1)两周。进行定量聚合酶链反应(QPCR)和蛋白质免疫印迹法检测炎症状态。对上述小鼠进行流式细胞术分析以检测免疫细胞激活情况。

结果

GML治疗减轻了DSS诱导的结肠炎小鼠的宏观症状,如结肠缩短、脾脏重量增加和体重减轻。此外,GML降低了促炎因子(NF-α、IL-1β和IL-1α)的表达,增加了抗炎因子(IL-10和TGF-β)的表达。GML抑制丝裂原活化蛋白激酶(MAPK)和核因子κB(NF-κB)信号通路的激活,改善组织损伤,并增加肠道紧密连接蛋白的表达。此外,通过流式细胞术从肠道组织中提取的淋巴细胞(LPMCs)显示,GML治疗导致辅助性T细胞17(Th17)细胞、中性粒细胞和巨噬细胞减少。16S核糖体DNA(rDNA)测序显示,GML增加了诸如阿克曼氏菌和鼠乳杆菌等共生菌的丰度。

结论

我们发现口服GML可通过抑制Th17细胞、中性粒细胞和巨噬细胞的浸润、保护肠道黏膜屏障及改变共生菌丰度来改善DSS诱导的结肠炎。本研究为GML在IBD治疗中的生物学功能和治疗潜力提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a24/9413164/f715df6a6dfa/fnut-09-911315-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a24/9413164/0ae6fe66e545/fnut-09-911315-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a24/9413164/a7a07bbf1439/fnut-09-911315-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a24/9413164/679789f39989/fnut-09-911315-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a24/9413164/698afb38655d/fnut-09-911315-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a24/9413164/f715df6a6dfa/fnut-09-911315-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a24/9413164/0ae6fe66e545/fnut-09-911315-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a24/9413164/a7a07bbf1439/fnut-09-911315-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a24/9413164/679789f39989/fnut-09-911315-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a24/9413164/698afb38655d/fnut-09-911315-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a24/9413164/f715df6a6dfa/fnut-09-911315-g0005.jpg

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