上海交通大学学报（医学版）

上海交通大学学报(医学版) ›› 2020, Vol. 40 ›› Issue (06): 744-751.doi: 10.3969/j.issn.1674-8115.2020.06.007

• 论著·基础研究 • 上一篇    下一篇

利拉鲁肽作用肠道固有淋巴细胞改善小鼠炎症性肠病

李 月1, 2，孙寒晓2，殳 洁2，李咏梅1#，盛慧明2#   

  1. 1. 北华大学医学院，吉林132013；2. 上海交通大学医学院附属同仁医院检验科，上海200336
  • 出版日期:2020-06-28 发布日期:2020-06-28
  • 通讯作者: 盛慧明，电子信箱：shm2783@shtrhospital.com。李咏梅，电子信箱：lymjyx@ 126.com。#为共同通信作者。
  • 作者简介:李 月(1994—)，女，检验师，硕士生；电子信箱：elfleeyue@163.com。
  • 基金资助:
    国家自然科学基金(81672083，81702071)。

Anti-inflammatory effects of liraglutide on innate lymphoid cells in mice with inflammatory bowel disease

LI Yue1, 2, SUN Han-xiao2, SHU Jie2, LI Yong-mei1#, SHENG Hui-ming2#   

  1. 1. Medical College of Beihua University, Jilin 132013, China; 2. Department of Laboratory Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
  • Online:2020-06-28 Published:2020-06-28
  • Supported by:
    National Natural Science Foundation of China (81672083, 81702071).

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摘要： 目的·明确胰高血糖素样肽-1受体激动剂(glucagon-like peptide-1 receptor agonist，GLP-1RA)利拉鲁肽在葡聚糖硫酸钠盐(dextran sulfate sodium，DSS)诱导的炎症性肠病(inflammatory bowel disease，IBD)中的作用及其机制。方法·使用DSS和无菌水配制成3% DSS的饮用水，小鼠自由饮用7 d，构建小鼠IBD模型。实验小鼠随机分为4组，分别为对照组［饮用无菌水，腹腔注射磷酸盐缓冲液（phosphate buffered saline，PBS）］、利拉鲁肽组（饮用无菌水，腹腔注射利拉鲁肽0.6 mg/kg）、模型组（饮用DSS水溶液，腹腔注射PBS）、治疗组（饮用DSS水溶液，腹腔注射利拉鲁肽0.6 mg/kg），每组各5只小鼠。实验中观察小鼠粪便形态、体质量变化、结肠长度，并应用苏木精-伊红（hematoxylin-eosin，H-E）染色观察小鼠结肠炎症程度，流式细胞术检测结肠内中性粒细胞、嗜酸性粒细胞比例以及固有淋巴细胞(innate lymphoid cell，ILC)分群和功能改变。结果·与模型组相比，治疗组小鼠粪便稀松、血便等症状明显改善，结肠长度缩短程度减轻（P=0.007），且H-E染色显示其结肠内炎症细胞浸润显著减少。流式细胞术分析结肠固有层细胞显示，与模型组相比，治疗组小鼠结肠内中性粒细胞比例明显降低（P=0.004），嗜酸性粒细胞比例明显降低（P=0.002）；2型ILC（group 2 ILC，ILC2）比例降低（P=0.032），3型ILC（group 3 ILC，ILC3）比例升高（P=0.008）；ILC3分泌的细胞因子白介素-22水平增加（P=0.008）。结论·利拉鲁肽通过影响ILC亚群比例及ILC3的分泌功能，延缓IBD的发生与发展。

关键词: 固有淋巴细胞, 炎症性肠病, 胰高血糖素样肽-1受体激动剂, 利拉鲁肽

Abstract:

Objective · To investigate the role and mechanism of glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide in dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD). Methods · The drinking water with DSS concentration of 3% was prepared by using DSS and sterile water, and the mice were free to drink for 7 days, to construct IBD model. The experimental mice were randomly divided into four groups with five mice in each group: the control group [drinking sterile water, intraperitoneal injection of phosphate buffered saline (PBS)], the liraglutide group (drinking sterile water, intraperitoneal injection of 0.6 mg/kg liraglutide), the model group (drinking DSS water solution, intraperitoneal injection of PBS) and the treatment group (drinking DSS water solution, intraperitoneal injection of 0.6 mg/kg liraglutide). During the experiment, the fecal morphology, body weight, and colon length were observed. And hematoxylin-eosin (H-E) staining was used to observe the degree of colitis in mice. Flow cytometry was used to detect the proportion of neutrophils and eosinophils, as well as the changes of the innate lymphoid cell (ILC) subsets and function in the colon. Results · Compared with the model group, the symptoms of loose stool and bloody stool were improved, and the shortened colon length was also improved (P=0.007) in the treatment group. H-E staining showed that the infiltration of inflammatory cells in the colon of the treatment group was significantly reduced. Flow cytometry analysis of the colonic lamina propria showed that the proportion of neutrophils in the colon of the treatment group was significantly reduced (P=0.004), and the proportion of eosinophils was also reduced (P=0.002); the proportion of ILC (ILC2) in group 2 decreased (P=0.032), but the proportion of ILC (ILC3) in group 3 increased (P=0.008); the cytokine interleukin-22 secreted by ILC3 was increased (P=0.008). Conclusion · Liraglutide may delay the development of IBD by affecting the proportion of ILC subsets and secretion function.

Key words: innate lymphoid cell (ILC), inflammatory bowel disease (IBD), glucagon-like peptide-1 receptor agonist (GLP-1RA), Liraglutide

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