| 肠上皮Metrnl基因敲除对肠道菌群以及溃疡性结肠炎的影响 |
| 投稿时间：2022-11-17 修订日期：2023-05-08 点此下载全文 |
| 引用本文：陈思敏,凌期盛,张赛龙,缪朝玉.肠上皮Metrnl基因敲除对肠道菌群以及溃疡性结肠炎的影响[J].药学实践杂志,2023,41(11):654~661 |
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| 基金项目:国家自然科学基金（81803541）；上海市“科技创新行动计划”实验动物项目（22140901900） |
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| 中文摘要:目的 探讨肠上皮Metrnl对葡聚糖硫酸钠盐（DSS）诱导的溃疡性结肠炎小鼠模型的作用及其对肠道菌群调节机制的影响。方法 应用不同浓度的DSS（3%和1%）对C57 小鼠进行造模，确定实验条件。给予肠上皮Metrnl特异性敲除小鼠（Metrnl(-/-)）及其对照小鼠（Metrnl(+/+)）3%DSS造模5 d，观察模型小鼠的生存时间、体重、疾病评分（DAI）、结肠长度以及结肠组织切片病理学变化等指标。使用16S核糖体RNA基因测序技术检测肠道菌群组成。结果 与1%DSS相比，3% DSS可显著缩短C57小鼠的生存时间（P<0.05），降低体重（P<0.05），增加DAI评分（P<0.05），缩短结肠长度（P<0.05），增加病理学评分（P<0.05）。给予3%DSS造模5 d后，与对照组Metrnl(+/+)小鼠相比，Metrnl(-/-)小鼠体重下降更多（P<0.05），DAI评分更高（P<0.05），结肠长度更短（P<0.05）以及病理学评分更高（P<0.05）。检测16S核糖体RNA结果显示，Metrnl(-/-)小鼠的肠道菌群多样性下降，拟杆菌（Bacteroidetes）和变形杆菌（Proteobacteria）显著降低，而厚壁菌（Firmicutes）显著升高。结论 Metrnl对3%DSS诱导的溃疡性结肠炎小鼠有保护作用，该作用可能与Metrnl对肠道菌群的调节作用相关。 |
| 中文关键词:Metrnl基因敲除 溃疡性结肠炎 肠道菌群 |
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| Effect of intestinal Metrnl gene knockout on intestinal microbiota and ulcerative colitis |
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| Abstract:Objective To investigate the effect of intestinal Metrnl on dextran sodium sulfate (DSS)-induced ulcerative colitis mouse model and the regulation mechanism of intestinal microbiota. Methods Different concentrations of DSS (3% DSS and 1% DSS) were used to induce ulcerative colitis on C57 mice to determine the experimental conditions. Intestinal epithelial Metrnl specific knockout mice (Metrnl(-/-)) and its control mice (Metrnl(+/+)) were administrated with 3% DSS for 5 d. Then the survival time, body weight, DAI (disease activity index), colon length and pathological changes in colon tissues were observed. 16S ribosomal RNA gene sequencing was used to detect the composition of intestinal microbiota. Results Compared with 1% DSS, 3% DSS could significantly aggravate ulcerative colitis on C57 mice, such as lower survival rate (P<0.05), more weight loss (P<0.05), higher DAI score (P<0.05), shorter colon length (P<0.05) and higher pathology score (P<0.05). After administrated to 3% DSS for 5 d, comparing with Metrnl(+/+) mice, Metrnl(-/-) mice showed more weight loss (P<0.05), higher DAI score (P<0.05), shorter colon length (P<0.05) and higher pathology score (P<0.05). The 16S ribosomal RNA results showed that the diversity of intestinal microbiota in Metrnl(-/-) mice significantly decreased. Furthermore, Bacteroidetes and Proteobacteria significantly decreased, while Firmicutes increased. Conclusion Metrnl could protect the DSS-induced ulcerative colitis mouse through regulating intestinal microbiota. |
| keywords:Metrnl gene knockout ulcerative colitis intestinal microbiota |
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