谷胱甘肽对小鼠的抗疲劳作用及其机制

本研究探讨了谷胱甘肽（glutathione，GSH）对小鼠的抗疲劳作用及机制。将小鼠随机分为正常对照组、运动疲劳组、GSH治疗组和西洋参对照组。在GSH治疗组和西洋参对照组中，每天运动前灌胃给予小鼠不同剂量的GSH（0.2、0.4、0.8?g/kg?mb）和西洋参（0.6?g/kg?mb），其余组灌胃生理盐水。给药和训练持续10?d。在最后1?d力竭游泳实验后立即处死小鼠，并测定生化指标；同时，采用免疫组织化学方法检测下丘脑室旁核（paraventricular?nucleus，PVN）c-fos免疫阳性细胞数。与运动疲劳组相比，GSH和西洋参均显著延长了小鼠运动时间（P＜0.05）；此外，GSH处理组小鼠血清中的血乳酸质量浓度、乳酸脱氢酶活力、肌酸磷酸激酶活力、尿素氮浓度以及肝脏中丙二醛含量显著降低（P＜0.05），而肝脏中的肝糖原和超氧化物歧化酶活力显著增加（P＜0.05）。在中枢疲劳实验中，GSH可以显著增加多巴胺质量浓度（P＜0.05），降低下丘脑中的5-羟色胺质量浓度并下调PVN中c-fos免疫阳性细胞的过度表达。高剂量GSH的抗疲劳效果与西洋参相比无显著性差异（P＞0.05）。GSH通过外周和中枢机制在小鼠体内具有明显的抗疲劳作用，可作为一种新的缓解运动性疲劳的药物。

Anti-fatigue Effect of Glutathione in Mice and Its Underlying Mechanisms

This study explored the anti-fatigue effect of glutathione (GSH) in mice and its underlying mechanisms. Mice were randomly divided into normal control, exercise-induced fatigue, GSH treatment and American ginseng (AG) control groups. The mice in the treatment groups were intragastrically administered with GSH (0.2, 0.4 and 0.8 g/kg mb) and AG (0.6 g/kg mb) daily before exercise, respectively, while the mice in the remaining groups were given normal saline. The experiment lasted for 10 days. The mice were sacrificed immediately after exhaustive swimming on the last day of the experiment to determine biochemical markers. The number of c-fos positive cells in the paraventricular nucleus (PVN) of the hypothalamus was measured by immunohistochemically. Compared with exercise-induced fatigue group, both GSH and AG significantly prolonged exhaustive swimming time (P < 0.05). Furthermore, the levels of blood lactic acid (LAC), lactic dehydrogenase (LDH) activity, blood urea nitrogen (BUN) and creatine phosphokinase (CK) activity in serum as well as malondialdehyde (MDA) content in liver decreased significantly (P < 0.05), while glycogen content and superoxide dismutase (SOD) activity in liver significantly increased in the GSH-treated mice (P < 0.05). With regard to central fatigue, GSH significantly increased dopamine (DA) content (P < 0.05), and decreased 5-hydroxytryptamine (5-HT) content in the hypothalamus and induced the over-expression of c-fos positive cells in the PVN. While the anti-fatigue effect of high-dose GSH was not significantly different from that of AG (P > 0.05), GSH had obvious anti-fatigue effect in mice via peripheral and central mechanisms, and could be used as a drug candidate for relieving exercise-induced fatigue.