Minaiyan Mohsen, Hajhashemi Valiollah, Rabbani Mohammad, Fattahian Ehsan, Mahzouni Parvin
Department of Pharmacology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Department of Pharmacology, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, I.R. Iran.
Res Pharm Sci. 2015 Jul-Aug;10(4):295-306.
Psychological disorders such as depression have more prevalence in inflammatory bowel disease patients and can exacerbate the clinical course of the disease, so anti-depressant therapy may have a potential to positively impact the disease course. On the other hand several antidepressant drugs have shown anti-inflammatory and immunomodulatory properties. Thus, this study aimed to explore the beneficial effects of venlafaxine on experimental colitis in normal and reserpinised depressed rats. Acetic acid colitis was induced in both reserpinised and non-reserpinised rats. Reserpinised groups received reserpine at dose of 6 mg/kg i.p.1 h prior to colitis induction and then treated with venlafaxine at doses of 10, 20, 40 mg/kg given i.p. 2 h after induction of colitis and daily for 4 consecutive days. Non-reserpinised groups treated with 10, 20, 40 mg/kg venlafaxine i.p. 2 h after the induction of colitis and daily for 4 successive days. Dexamethasone (1 mg/kg, i.p.) was used as reference drug. Colonic inflammation was evaluated using macroscopic, histological and myeloperoxidase activity measurements. Results showed that reserpine at dose of 6 mg/kg exacerbated the colitis damage. Compared to acetic acid control, venlafaxine at dose of 40 mg/kg as well as dexamethasone significantly improved colitis parameters in both reserpinised and non-reserpinised animals. Venlafaxine reduced inflammatory injury in this animal model of induced ulcerative colitis. These effects are probably mediated first through depressive behavioral changes that could be mediated through the brain-gut axis and second for the anti-inflammatory effect of the drug.
抑郁症等心理障碍在炎症性肠病患者中更为普遍,并且会加剧疾病的临床进程,因此抗抑郁治疗可能对疾病进程产生积极影响。另一方面,几种抗抑郁药物已显示出抗炎和免疫调节特性。因此,本研究旨在探讨文拉法辛对正常和利血平化抑郁大鼠实验性结肠炎的有益作用。在利血平化和未利血平化的大鼠中均诱导了乙酸结肠炎。利血平化组在诱导结肠炎前1小时腹腔注射6mg/kg利血平,然后在诱导结肠炎后2小时腹腔注射10、20、40mg/kg文拉法辛,并连续4天每日给药。未利血平化组在诱导结肠炎后2小时腹腔注射10、20、40mg/kg文拉法辛,并连续4天每日给药。地塞米松(1mg/kg,腹腔注射)用作参考药物。使用宏观、组织学和髓过氧化物酶活性测量来评估结肠炎症。结果表明,6mg/kg剂量的利血平加剧了结肠炎损伤。与乙酸对照组相比,40mg/kg剂量的文拉法辛以及地塞米松在利血平化和未利血平化的动物中均显著改善了结肠炎参数。文拉法辛减轻了这种诱导性溃疡性结肠炎动物模型中的炎症损伤。这些作用可能首先通过可能由脑-肠轴介导的抑郁行为变化介导,其次是通过药物的抗炎作用介导。