Motaghi Ehsan, Hajhashemi Valiollah, Mahzouni Parvin, Minaiyan Mohsen
Department of Pharmacology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Clinical Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Iran J Pharm Res. 2019 Summer;18(3):1341-1850. doi: 10.22037/ijpr.2019.1100751.
Ulcerative colitis is chronic and recurrent disease of the gastrointestinal tract with uncertain etiology and incomplete treatment options. N-methyl-d-aspartate (NMDA) receptor suppression has shown anti-inflammatory effects and . The aim of present study was to evaluate the role of dizocilpine (MK-801), a noncompetitive NMDA receptor antagonist, on TNBS (trinitrobenzene sulfonic acid)-induced murine model of colitis. Dizocilpine (0.1, 1 and 5 mg/kg) was given to mice intraperitoneally from 24 h before induction of colitis and daily thereafter for 4 days. Dexamethasone (1 mg/kg) was used as the reference drug. Colitis was induced by intracolonic administration of TNBS/Ethanol (50/50 v/v, 40mg/kg). Animals were sacrificed 5 days after colitis induction and distal colons were examined macroscopically and microscopically. The colonic tissue level of pro-inflammatory cytokines including interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were assessed by ELISA. Myeloperoxidase (MPO) level was also measured in colon. Dizocilpine, particularly with intermediate dose of 1mg/kg significantly improved animal's weight loss as well as macroscopic and microscopic signs of colitis, reduced colonic levels of IL-1β, IL-6, TNF-α and MPO activity. Hence, dizocilpine has significant protective effects in TNBS-induced colitis and NMDA suppression may be a new and effective therapeutic strategy in ulcerative colitis via decreasing in pro-inflammatory cytokine production.
溃疡性结肠炎是一种病因不明且治疗方案不完善的慢性复发性胃肠道疾病。N-甲基-D-天冬氨酸（NMDA）受体抑制已显示出抗炎作用。本研究的目的是评估非竞争性NMDA受体拮抗剂地佐环平（MK-801）对三硝基苯磺酸（TNBS）诱导的小鼠结肠炎模型的作用。在诱导结肠炎前24小时给小鼠腹腔注射地佐环平（0.1、1和5mg/kg），此后每天注射一次，共4天。地塞米松（1mg/kg）用作参考药物。通过结肠内注射TNBS/乙醇（50/50 v/v，40mg/kg）诱导结肠炎。在诱导结肠炎5天后处死动物，对远端结肠进行宏观和微观检查。通过酶联免疫吸附测定法评估包括白细胞介素1β（IL-1β）、白细胞介素6（IL-6）和肿瘤坏死因子-α（TNF-α）在内的促炎细胞因子的结肠组织水平。还测量了结肠中的髓过氧化物酶（MPO）水平。地佐环平，特别是中等剂量1mg/kg，显著改善了动物的体重减轻以及结肠炎的宏观和微观体征，降低了结肠中IL-1β、IL-6、TNF-α水平和MPO活性。因此，地佐环平在TNBS诱导的结肠炎中具有显著的保护作用，抑制NMDA可能是通过减少促炎细胞因子产生治疗溃疡性结肠炎的一种新的有效治疗策略。
