Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh-160014, India.
Pharmacol Rep. 2012;64(6):1326-36. doi: 10.1016/s1734-1140(12)70930-1.
Chronic fatigue stress (CFS) is an important health problem with unknown causes and unsatisfactory prevention strategies, often characterized by long-lasting and debilitating fatigue, myalgia, impairment of neuro-cognitive functions along with other common symptoms. The present study has been designed to explore the protective effect of statins against running wheel activity induced fatigue anxiety.
Male albino Laca mice (20-30 g) were subjected to swim stress induced fatigue in a running wheel activity apparatus. Atorvastatin (10, 20 mg/kg, po) and fluvastatin (5, 10 mg/kg, po) were administered daily for 21 days, one hour prior to the animals being subjected to running wheel activity test session of 6 min. Various behavioral tests (running wheel activity, locomotor activity and elevated plus maze test), biochemical parameters (lipid peroxidation, nitrite concentration, glutathione levels and catalase activity) and mitochondrial complex enzyme dysfunctions (complex I, II, III and IV) were subsequently assessed.
Animals exposed to 6 min test session on running wheel for 21 days showed a significant decrease in number of wheel rotations per 6 min indicating fatigue stress like behavior. Treatment with atorvastatin (10 and 20 mg/kg) and fluvastatin (10 mg/kg) for 21 days significantly improved the behavioral alterations [increased number of wheel rotations and locomotor activity, and anxiety like behavior (decreased number of entries and time spent in open arm)], oxidative defence and mitochondrial complex enzyme activities in brain.
Present study suggests the protective role of statins against chronic fatigue induced behavioral, biochemical and mitochondrial dysfunctions.
慢性疲劳应激（CFS）是一种重要的健康问题，其病因不明，预防策略也不尽人意，常表现为持久的、使人虚弱的疲劳、肌痛、神经认知功能障碍以及其他常见症状。本研究旨在探讨他汀类药物对跑轮活动诱导的疲劳焦虑的保护作用。
雄性白化 Laca 小鼠（20-30 克）在跑轮活动装置中进行游泳应激诱导的疲劳。阿托伐他汀（10、20mg/kg，po）和氟伐他汀（5、10mg/kg，po）每天给药一次，共 21 天，在动物进行 6 分钟跑轮活动测试前一小时给药。随后评估了各种行为测试（跑轮活动、运动活性和高架十字迷宫测试）、生化参数（脂质过氧化、亚硝酸盐浓度、谷胱甘肽水平和过氧化氢酶活性）和线粒体复合酶功能障碍（复合物 I、II、III 和 IV）。
连续 21 天在跑轮上进行 6 分钟测试的动物，其每 6 分钟的轮数明显减少，表明出现了类似疲劳的行为。阿托伐他汀（10 和 20mg/kg）和氟伐他汀（10mg/kg）连续 21 天治疗可显著改善行为改变[增加轮数和运动活性，以及焦虑样行为（进入次数和开放臂停留时间减少）]、氧化防御和大脑线粒体复合酶活性。
本研究提示他汀类药物对慢性疲劳引起的行为、生化和线粒体功能障碍具有保护作用。
