Protective effects of selective and non-selective cyclooxygenase inhibitors in an animal model of chronic stress  

选择性和非选择性环氧合酶抑制剂对慢性压力小鼠模型具有保护作用(英文)

作　　者：Anil Kumar Beenta Kumari Puneet Kumar 

机构地区：[1]Panjab大学药物科学研究所药理学部,UGC高级研究中心

出　　处：《Neuroscience Bulletin》2010年第1期17-27,共11页神经科学通报（英文版）

摘　　要：Objective Cyclooxygenase isoenzyme is known to be expressed in different regions of brain, and is mainly used for the treatment of pain and inflammation. Recently, it is proposed that cyclooxygenase isoenzyme may also play a key role in the pathophysiology of various brain-related disorders. The present study was aimed to explore the protective effect of cyclooxygenase inhibitors on stress by using an animal model of chronic stress. Methods The animals were forced to swim individually for a period of 6 min every day for 15 d. Then, the behavior （locomotor activity, anxiety and memory） and biochemical （lipid peroxidation, nitrite level, reduced glutathione, and catalase） alterations were assessed. Results Forced swimming for 15 d caused impaired locomotor activity, anxiety-like behavior and decreased percentage of memory retention, as compared to na？ve mice （without chronic fatigue treatment）. Biochemical analysis revealed significant increases in lipid peroxidation and nitrite level, while levels of reduced glutathione and catalase activity were both decreased. Chronic treatment with naproxen （14 mg/kg, i.p.）, rofecoxib （5 mg/kg, i.p.）, meloxicam （5 mg/kg, i.p.）, nimesulide （5 mg/kg, i.p.） and valdecoxib （10 mg/kg, i.p.） significantly attenuated these behavioral and biochemical （oxidative damage） alterations in chronic-stressed mice. Conclusion The cyclooxygenase inhibitors could be used in the management of chronic fatigue-like conditions.目的环氧合酶是广泛表达于大脑各区域的一类同功酶,主要用于治疗疼痛与炎症。最近研究还发现环氧合酶在大脑相关疾病的病理生理过程中扮演关键角色。本文运用慢性压力动物模型,对环氧合酶抑制剂的保护作用做一探讨。方法每只小鼠每天被迫游泳 6 min,共持续 15 天。结束后进行行为学(包括活动能力、焦虑以及记忆能力)和生化指标(包括脂质过氧化、亚硝酸盐水平、还原性型谷胱甘肽和过氧化氢酶水平)的检测。结果持续15天的强迫性游泳会损伤小鼠活动能力,引起焦虑样行为的产生,并削弱记忆力。在生化指标方面,脂质过氧化和亚硝酸盐水平均显著提高,还原型谷胱甘肽和过氧化氢酶活力则显著降低。此外,环氧合酶抑制剂,包括甲氧萘丙酸、罗非考昔、美洛昔康、尼美舒利和伐地考昔,都能显著减缓这些损伤。结论环氧合酶抑制剂可被用来治疗慢性疲劳综合症。

关 键 词：chronic fatigue syndrome NAPROXEN VALDECOXIB ROFECOXIB NIMESULIDE MELOXICAM 

分 类 号：R96[医药卫生—药理学]