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丙戊酸钠对大鼠乙酸诱导性结肠炎的影响。

The effect of sodium valproate on acetic acid-induced colitis in rats.

作者信息

Najafi Ali, Motaghi Ehsan, Hosseini Mohammad Javad, Ghasemi-Pirbaluti Masoumeh

机构信息

Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Department of Physiology and Pharmacology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.

出版信息

Inflammopharmacology. 2017 Feb;25(1):137-145. doi: 10.1007/s10787-016-0304-1. Epub 2016 Dec 31.

Abstract

Ulcerative colitis is a chronic recurrent disease with incomplete treatment options. The current article evaluated the effect of sodium valproate on acetic acid-induced ulcerative colitis in rats. Rats were randomly distributed into six groups including Sham group, colitis control group, sodium valproate treatment groups (50, 100 and 300 mg/kg, i.p.) and dexamethasone-treatment group. Dexamethasone was used as a reference drug. Colitis was induced by intracolonic instillation of 2 mL of 3% acetic acid solution. The efficacy of sodium valproate was evaluated by macroscopical and histopathological scoring systems, hematocrit measurement as well as biochemical analysis including myeloperoxidase (MPO) and pro-inflammatory cytokines assessment. Sodium valproate, particularly with doses of 100 and 300 mg/kg significantly improved weight loss, and macroscopic damage, reduced ulcer area, colon weight, microscopic colitis index and elevated hematocrit level. Biochemical experiments showed elevated levels of colonic MPO activity, interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in colitis control group. Treatment with sodium valproate at the doses of 100 and 300 mg/Kg) decreased the MPO activity and colonic concentrations of IL-1β, IL-6 and TNF-α. The results provide evidence that sodium valproate has a protective effect in acetic acid-induced ulcerative colitis which might be due to its anti-inflammatory activities, and it may be useful in patients with ulcerative colitis.

摘要

溃疡性结肠炎是一种治疗方案不完善的慢性复发性疾病。本文评估了丙戊酸钠对乙酸诱导的大鼠溃疡性结肠炎的影响。大鼠被随机分为六组,包括假手术组、结肠炎对照组、丙戊酸钠治疗组(50、100和300mg/kg,腹腔注射)和地塞米松治疗组。地塞米松用作参考药物。通过向结肠内注入2mL 3%乙酸溶液诱导结肠炎。通过宏观和组织病理学评分系统、血细胞比容测量以及包括髓过氧化物酶(MPO)和促炎细胞因子评估在内的生化分析来评估丙戊酸钠的疗效。丙戊酸钠,特别是剂量为100和300mg/kg时,显著改善了体重减轻和宏观损伤,减小了溃疡面积、结肠重量、微观结肠炎指数并提高了血细胞比容水平。生化实验表明,结肠炎对照组结肠MPO活性、白细胞介素1β(IL-1β)、白细胞介素6(IL-6)和肿瘤坏死因子-α(TNF-α)水平升高。以100和300mg/Kg剂量的丙戊酸钠治疗降低了MPO活性以及结肠中IL-1β、IL-6和TNF-α的浓度。结果提供了证据表明丙戊酸钠对乙酸诱导的溃疡性结肠炎具有保护作用,这可能归因于其抗炎活性,并且它可能对溃疡性结肠炎患者有用。

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