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米诺环素在实验性结肠炎中的肠道抗炎作用与其免疫调节和抗菌特性均有关。

The intestinal anti-inflammatory effect of minocycline in experimental colitis involves both its immunomodulatory and antimicrobial properties.

机构信息

Centro de Investigaciones Biomédicas en Red - Enfermedades Hepáticas y Digestivas (CIBER-EHD), Department of Pharmacology, Center for Biomedical Research, University of Granada, Avenida del Conocimiento s/n, 18100 Armilla, Granada, Spain.

出版信息

Pharmacol Res. 2011 Apr;63(4):308-19. doi: 10.1016/j.phrs.2010.12.011. Epub 2010 Dec 28.

Abstract

Some antibiotics, including minocycline, have recently been reported to display immunomodulatory properties in addition to their antimicrobial activity. The use of a compound with both immunomodulatory and antibacterial properties could be very interesting in the treatment of inflammatory bowel disease (IBD), so the aim of our study was to evaluate the anti-inflammatory effect of minocycline in several experimental models of IBD. Firstly, the immunomodulatory activity of the antibiotic was tested in vitro using Caco-2 intestinal epithelial cells and RAW 264.7 macrophages; minocycline was able to inhibit IL-8 and nitrite production, respectively. In vivo studies were performed in trinitrobenzenesulfonic acid (TNBS)-induced rat colitis and dextran sodium sulfate (DSS)-induced mouse colitis. The results revealed that minocycline exerted an intestinal anti-inflammatory effect when administered as a curative treatment in the TNBS model, modulating both immune and microbiological parameters, being confirmed in the DSS model; whereas none of the other antibiotics tested (tetracycline and metronidazole) showed anti-inflammatory effect. However, minocycline administration before the colitis induction was not able to prevent the development of the intestinal inflammation, thus showing that only its antimicrobial activity is not enough for the anti-inflammatory effect. In conclusion, minocycline displays an anti-inflammatory effect on different models of rodent colitis which could be attributed to the association of its antibacterial and immunomodulatory properties.

摘要

一些抗生素,包括米诺环素,除了具有抗菌活性外,最近还被报道具有免疫调节特性。在治疗炎症性肠病(IBD)方面,使用具有免疫调节和抗菌特性的化合物可能非常有趣,因此我们的研究旨在评估米诺环素在几种 IBD 实验模型中的抗炎作用。首先,使用 Caco-2 肠上皮细胞和 RAW 264.7 巨噬细胞在体外测试了抗生素的免疫调节活性;米诺环素能够分别抑制 IL-8 和亚硝酸盐的产生。在三硝基苯磺酸(TNBS)诱导的大鼠结肠炎和葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎中进行了体内研究。结果表明,米诺环素在 TNBS 模型中作为治疗性药物给药时发挥肠道抗炎作用,调节免疫和微生物学参数,在 DSS 模型中得到证实;而测试的其他抗生素(四环素和甲硝唑)均未显示抗炎作用。然而,米诺环素在结肠炎诱导前给药不能预防肠道炎症的发展,因此表明仅其抗菌活性不足以产生抗炎作用。总之,米诺环素对不同的啮齿动物结肠炎模型表现出抗炎作用,这可能归因于其抗菌和免疫调节特性的联合作用。

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