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氟伏沙明对正常和利血平化抑郁大鼠乙酸诱导结肠炎的抗结肠炎作用评价。

Evaluation of anti-colitic effect of fluvoxamine against acetic acid-induced colitis in normal and reserpinized depressed rats.

作者信息

Minaiyan Mohsen, Hajhashemi Valiollah, Rabbani Mohammad, Fattahian Ehsan, Mahzouni Parvin

机构信息

Department of Pharmacology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

Department of Pharmacology and Physiology, School of Medicine, Shahrekord University of Medical Sciences, P.O. Box 8815774667, Shahrekord, Iran.

出版信息

Eur J Pharmacol. 2015 Jan 5;746:293-300. doi: 10.1016/j.ejphar.2014.11.016. Epub 2014 Nov 25.

Abstract

High prevalence of psychological comorbidities such as depression and anxiety in patients with inflammatory bowel disease (IBD) supports the premise that adding an anti-depressant drug with known anti-inflammatory effect to the medical treatment have beneficial effect in the course of the underlying disease. Colitis was induced by intracolonic instillation of 2 ml of 4% v/v acetic acid solution in rats. Anti-colitic effect of fluvoxamine was evaluated in two categories: A: normal rats, B: reserpinized (6 mg/kg, i.p.) depressed rats. In group A, fluvoxamine (2.5, 5, 10 mg/kg, i.p.) was administered 2 h after induction of colitis and in group B: reserpine (6 mg/kg, i.p.) was administered 1 h prior to colitis induction and then fluvoxamine (2.5, 5, 10 mg/kg, i.p.) was administered 2 h after colitis induction. Dexamethasone (1 mg/kg) was used as reference drug. All the treatments continued daily for five days. The effect was assessed on the basis of macroscopic score, biochemical (myeloperoxidase) changes and histopathological studies. Results showed that fluvoxamine (2.5 and 5 mg/kg) and dexamethasone treatment markedly reduced disease severity in both reserpinized and non-reserpinized rats as indicated by reduction in macroscopic and microscopic colonic damages while reserpine adversely exacerbated the colitis damage. Myeloperoxidase activity which was increased following colitis induction was also decreased. The findings of this study elucidate the anti-colitic and anti-inflammatory properties of fluvoxamine and so introduced it as a good candidate to treat depressive symptoms in people comorbid to IBD.

摘要

炎症性肠病(IBD)患者中抑郁症和焦虑症等心理合并症的高患病率支持了这样一个前提,即在治疗中添加具有已知抗炎作用的抗抑郁药物对基础疾病的病程具有有益效果。通过向大鼠结肠内注入2 ml 4% v/v乙酸溶液诱导结肠炎。在两类大鼠中评估氟伏沙明的抗结肠炎作用:A组:正常大鼠;B组:利血平化(6 mg/kg,腹腔注射)的抑郁大鼠。在A组中,结肠炎诱导后2小时给予氟伏沙明(2.5、5、10 mg/kg,腹腔注射);在B组中,在结肠炎诱导前1小时给予利血平(6 mg/kg,腹腔注射),然后在结肠炎诱导后2小时给予氟伏沙明(2.5、5、10 mg/kg,腹腔注射)。地塞米松(1 mg/kg)用作参考药物。所有治疗每天持续五天。根据宏观评分、生化(髓过氧化物酶)变化和组织病理学研究评估效果。结果表明,氟伏沙明(2.5和5 mg/kg)和地塞米松治疗显著降低了利血平化和未利血平化大鼠的疾病严重程度,这表现为宏观和微观结肠损伤的减轻,而利血平则加剧了结肠炎损伤。结肠炎诱导后增加的髓过氧化物酶活性也降低了。本研究结果阐明了氟伏沙明的抗结肠炎和抗炎特性,因此将其作为治疗IBD合并症患者抑郁症状的良好候选药物。

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