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γ-氨基丁酸能机制可能参与褪黑素对睡眠剥夺诱导的小鼠行为改变和氧化损伤的保护作用。

Possible involvement of GABAergic mechanism in protective effect of melatonin against sleep deprivation-induced behavior modification and oxidative damage in mice.

作者信息

Kumar Anil, Singh Anant, Kumar Puneet

机构信息

Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160 014, India.

出版信息

Indian J Exp Biol. 2011 Mar;49(3):211-8.

PMID:21452601
Abstract

Sleep deprivation for 72 h caused anxiety like behavior, weight loss, impaired locomotor activity and oxidative damage as indicated by increase in lipid peroxidation, nitrite level and depletion of reduced glutathione and catalase activity in sleep deprived mice brain. Treatment with melatonin (5 and 10 mg/kg, ip) significantly improved locomotor activity, weight loss and antianxiety effect as compared to control (sleep deprived). Biochemically, melatonin treatment significantly restored depleted reduced glutathione, catalase activity, attenuated lipid peroxidation and nitrite level as compared to control (72 h sleep-deprived) animals. A combination of flumazenil (0.5 mg/kg, ip) and picrotoxin (0.5 mg/kg, ip) with lower dose of melatonin (5 mg/kg, ip) significantly antagonized the protective effect of melatonin. However, combination of muscimol (0.05 mg/kg, ip) with melatonin (5 mg/kg, ip) potentiated protective effect of melatonin as compared to their effect per se. The results suggest that melatonin may produce its protective effect by involving GABAergic system against sleep deprivation-induced anxiety like behavior and related oxidative damage.

摘要

睡眠剥夺72小时会导致小鼠出现类似焦虑的行为、体重减轻、运动活动受损以及氧化损伤,这表现为睡眠剥夺小鼠大脑中脂质过氧化增加、亚硝酸盐水平升高、还原型谷胱甘肽耗竭以及过氧化氢酶活性降低。与对照组(睡眠剥夺组)相比,褪黑素(5和10毫克/千克,腹腔注射)治疗显著改善了运动活动、体重减轻和抗焦虑作用。从生化角度来看,与对照组(睡眠剥夺72小时)动物相比,褪黑素治疗显著恢复了耗竭的还原型谷胱甘肽、过氧化氢酶活性,减轻了脂质过氧化和亚硝酸盐水平。氟马西尼(0.5毫克/千克,腹腔注射)和印防己毒素(0.5毫克/千克,腹腔注射)与低剂量褪黑素(5毫克/千克,腹腔注射)联合使用显著拮抗了褪黑素的保护作用。然而,与它们本身的作用相比,蝇蕈醇(0.05毫克/千克,腹腔注射)与褪黑素(5毫克/千克,腹腔注射)联合使用增强了褪黑素的保护作用。结果表明,褪黑素可能通过涉及γ-氨基丁酸能系统来产生其对睡眠剥夺诱导的类似焦虑行为和相关氧化损伤的保护作用。

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