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结肠 M1 巨噬细胞与万古霉素处理的小鼠胃肠道运动延长和肥胖有关。

Colonic M1 macrophage is associated with the prolongation of gastrointestinal motility and obesity in mice treated with vancomycin.

机构信息

Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663‑8501, Japan.

出版信息

Mol Med Rep. 2019 Apr;19(4):2591-2598. doi: 10.3892/mmr.2019.9920. Epub 2019 Jan 31.

Abstract

Gut microbiota plays a pivotal role in not only the gastrointestinal (GI) immune system but also GI motility and metabolism. Antibiotic treatments are likely to affect the gut flora and GI immune system, subsequently disturbing GI motility and body metabolism. In the present study, we investigated antibiotic‑induced alterations of body metabolism and GI motility in association with the macrophage profile in the colon. Specific pathogen‑free (SPF) mice (ICR; 6 weeks old; female) were orally administered vancomycin (0.2 mg/ml) in drinking water for 5 weeks, and subsequent changes in pathophysiology were observed. The expression of CD80 and CD163 was examined by immunohistochemistry and the expression of cytokines in colonic tissues was evaluated by reverse transcription‑quantitative polymerase chain reaction. The gastrointestinal transit time (GITT) was measured by administration of carmine red (6% w/v) solution. In the vancomycin‑treated SPF mice, significant increases in body weight, cecum weight and GITT were observed compared with the controls. The number of CD80‑positive M1 macrophages and the expression of interferon‑γ and interleukin‑12 were significantly increased, whereas, the numbers of CD163‑positive M2 macrophages in the mucosal and muscular layers were decreased in the colon of vancomycin‑treated mice. GITT was positively correlated with the number of CD80‑positive M1 macrophages in the colonic mucosa; however, was negatively correlated with the number of CD163‑positive M2 macrophages in the mucosal and muscular layers. Therefore, it was suggested that antibiotic treatment affects body metabolism and GI motility, accompanied by alterations in macrophage polarization and cytokine profiles in the colon.

摘要

肠道微生物群不仅在胃肠道 (GI) 免疫系统中发挥关键作用,而且在 GI 运动和代谢中也发挥关键作用。抗生素治疗可能会影响肠道菌群和 GI 免疫系统,随后扰乱 GI 运动和身体代谢。在本研究中,我们研究了抗生素诱导的身体代谢和 GI 运动的改变与结肠中的巨噬细胞表型之间的关联。将无菌 (SPF) 小鼠 (ICR;6 周龄;雌性) 经口给予饮用水中的万古霉素 (0.2mg/ml) 5 周,观察随后的病理生理学变化。通过免疫组织化学检查 CD80 和 CD163 的表达,并通过逆转录定量聚合酶链反应评估结肠组织中细胞因子的表达。通过给予胭脂红 (6%w/v) 溶液测量胃肠道转运时间 (GITT)。在万古霉素处理的 SPF 小鼠中,与对照组相比,体重、盲肠重量和 GITT 显著增加。CD80 阳性 M1 巨噬细胞数量和干扰素-γ和白细胞介素-12 的表达显著增加,而在万古霉素处理的小鼠结肠中,粘膜和肌肉层中的 CD163 阳性 M2 巨噬细胞数量减少。GITT 与结肠粘膜中 CD80 阳性 M1 巨噬细胞的数量呈正相关;然而,与粘膜和肌肉层中 CD163 阳性 M2 巨噬细胞的数量呈负相关。因此,建议抗生素治疗会影响身体代谢和 GI 运动,同时伴有结肠中巨噬细胞极化和细胞因子谱的改变。

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