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环丙沙星对三硝基苯磺酸诱导的小鼠结肠炎的免疫调节作用。

Immunomodulatory effects of ciprofloxacin in TNBS-induced colitis in mice.

作者信息

Lahat Guy, Halperin Drora, Barazovsky Eli, Shalit Itamar, Rabau Micha, Klausner Josef, Fabian Ina

机构信息

Department of Surgery, Sourasky Medical Center, Tel-Aviv, Israel.

出版信息

Inflamm Bowel Dis. 2007 May;13(5):557-65. doi: 10.1002/ibd.20077.

Abstract

BACKGROUND

Crohn's exacerbation and pouchitis are commonly treated with ciprofloxacin and metronidazole. Few studies have shown an advantage of this regimen compared with other antibiotics. Most attributed the effect to its better antibacterial coverage. Others have shown an apparent anti-inflammatory effect of quinolones in several in vitro and in vivo models of inflammation other than inflammatory bowel diseases (IBD). Our objective was to test the hypothesis that ciprofloxacin may act as an anti-inflammatory agent rather than just an antibacterial drug using a model of chemical colitis.

METHODS

TNBS colitis was induced in BALB/c mice. The anti-inflammatory effect of ciprofloxacin compared with ceftazidime and dexamethasone was assessed.

RESULTS

Mice treated with ciprofloxacin (7.5 mg/kg or 15 mg/kg) had significant reductions in clinical signs, body weight loss, splenic and colonic weight increase compared with saline-treated and ceftazidime-treated mice. Histologic analysis showed mild inflammation in ciprofloxacin-treated mice with a mean score of 3.8 +/- 0.5 points compared with moderate colitis scored 7.8 +/- 1.3 and 9.5 +/- 0.5 points in saline and ceftazidime-treated mice, respectively. Analysis of cytokine levels in colon homogenates showed a significant decrease of IL-1beta, IL-8, and TNFalpha levels in ciprofloxacin-treated animals. Immunohistochemistry for NFkappaB showed strong positivity in saline and ceftazidime-treated mice in contrast to weak focal stain in ciprofloxacin- and dexamethasone-treated mice.

CONCLUSIONS

These findings imply that ciprofloxacin has an anti-inflammatory effect, rather than just an antibacterial one, making its use favorable in IBD patients.

摘要

背景

克罗恩病发作和袋炎通常用环丙沙星和甲硝唑治疗。与其他抗生素相比,很少有研究显示该方案具有优势。大多数人将其效果归因于更好的抗菌覆盖范围。其他人在几种非炎症性肠病(IBD)的体外和体内炎症模型中显示了喹诺酮类药物明显的抗炎作用。我们的目的是使用化学性结肠炎模型来检验环丙沙星可能作为一种抗炎剂而非仅仅是抗菌药物的假设。

方法

在BALB/c小鼠中诱导三硝基苯磺酸(TNBS)结肠炎。评估环丙沙星与头孢他啶和地塞米松相比的抗炎效果。

结果

与生理盐水处理组和头孢他啶处理组的小鼠相比,用环丙沙星(7.5毫克/千克或15毫克/千克)治疗的小鼠在临床症状、体重减轻、脾脏和结肠重量增加方面有显著降低。组织学分析显示,环丙沙星处理组小鼠有轻度炎症,平均评分为3.8±0.5分,而生理盐水处理组和头孢他啶处理组小鼠分别为中度结肠炎,评分为7.8±1.3分和9.5±0.5分。结肠匀浆中细胞因子水平分析显示,环丙沙星处理的动物中白细胞介素-1β(IL-1β)、白细胞介素-8(IL-8)和肿瘤坏死因子-α(TNFα)水平显著降低。核因子κB(NFκB)的免疫组织化学显示,生理盐水和头孢他啶处理组小鼠呈强阳性,而环丙沙星和地塞米松处理组小鼠呈弱局灶性染色。

结论

这些发现表明环丙沙星具有抗炎作用,而非仅仅是抗菌作用,这使其在IBD患者中的应用具有优势。

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