5-HT3 受体参与曲匹司特对实验性 TNBS 诱导的大鼠结肠炎的抗炎作用。
Involvement of 5HT3 Receptors in Anti-Inflammatory Effects of Tropisetron on Experimental TNBS-Induced Colitis in Rat.
机构信息
Department of Pharmacology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
出版信息
Bioimpacts. 2013;3(4):169-76. doi: 10.5681/bi.2013.021. Epub 2013 Jun 18.
INTRODUCTION
There is a pressing need for research leading to the development of new effective drugs with lower side effects and more efficacy for treating inflammatory bowel disease (IBD). The analgesic and anti-inflammatory properties of 5-Hydroxytryptamine (5-HT)-3 receptor antagonists have been shown in in vivo and in vitro studies. The present study was designed to investigate the effects of tropisetron, a 5-HT3 receptor antagonist, on an immune-based animal model of IBD.
METHODS
In the present study, the trinitrobenzenesulfonic acid (TNBS) model of colitis in the rat was used. Two hours after induction of colitis in rats, tropisetron (2 mg/kg), dexamethasone (1 mg/kg), meta-chlorophenylbiguanide (mCPBG, 5 mg/kg), a 5-HT3 receptor agonist, or tropisetron + mCPBG were intraperitoneally (i.p.) administrated for 6 days. Animals were then sacrificed; macroscopic, histological, biochemical (myeloperoxidase [MPO]) assessments and ELISA test (tumor necrosis factor-alpha, interleukin-6 and interleukin-1 beta) were performed on distal colon samples.
RESULTS
Tropisetron or dexamethasone treatment significantly reduced macroscopic and microscopic colonic damages. In addition, a significant reduction in MPO activity and colonic levels of inflammatory cytokines was seen. The beneficial effects of tropisetron were antagonized by concurrent administration of mCPBG.
CONCLUSION
The present study indicates that the protective effects of tropisetron on TNBS-induced colitis can be mediated by 5-HT3 receptors.
简介
目前迫切需要研究开发副作用更低、疗效更高的治疗炎症性肠病（IBD）的新有效药物。5-羟色胺（5-HT）-3 受体拮抗剂在体内和体外研究中均显示出具有镇痛和抗炎作用。本研究旨在研究 5-HT3 受体拮抗剂托烷司琼对基于免疫的 IBD 动物模型的影响。
方法
本研究采用大鼠三硝基苯磺酸（TNBS）结肠炎模型。在大鼠结肠炎诱导后 2 小时，托烷司琼（2mg/kg）、地塞米松（1mg/kg）、间氯苯胍（mCPBG，5mg/kg）、5-HT3 受体激动剂或托烷司琼+mCPBG 经腹腔（i.p.）给药 6 天。然后处死动物；对远端结肠样本进行宏观、组织学、生化（髓过氧化物酶 [MPO]）评估和 ELISA 检测（肿瘤坏死因子-α、白细胞介素-6 和白细胞介素-1β）。
结果
托烷司琼或地塞米松治疗可显著减轻结肠的宏观和微观损伤。此外，MPO 活性和结肠炎症细胞因子水平也显著降低。mCPBG 同时给药拮抗了托烷司琼的有益作用。
结论
本研究表明，托烷司琼对 TNBS 诱导的结肠炎的保护作用可能通过 5-HT3 受体介导。
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