Wu Ya-Nan, Ma Qing, Wang Yan-Yan, Huang Li-Li
College of Pharmacy,Heilongjiang University of Chinese Medicine,Harbin 150040,China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2024 Aug;46(4):471-481. doi: 10.3881/j.issn.1000-503X.15910.
Objective To investigate the effects of Schisandrae Chinensis Fructus lignans on the alertness of the rats with sleep deprived by treadmill exercise and the underlying neurobiological mechanism. Methods According to the random number table method,SD male rats were assigned into control,sleep deprivation,low-,medium-,and high-dose Schisandrae Chinensis Fructus lignans,and atomoxetine hydrochloride groups,with 8 rats in each group.The rats in other groups except the control group were subjected to sleep deprivation by treadmill exercise for 3 d.During the deprivation period,each administration group was administrated with the corresponding drug by gavage,and a 5-9 hole tester was used to test the alertness performance of rats in each group. Furthermore,other SD male rats were selected and randomized into control,sleep deprivation,Schisandrae Chinensis Fructus lignans (67.2 mg/kg) and atomoxetine hydrochloride groups,with 10 rats in each group.The rats were modeled with the sleep deprivation method the same as that above and administrated with corresponding agents.ELISA was employed to measure the serum level of orexin A in each group of rats.The protein levels of c-Fos,orexin receptor 1,and orexin receptor 2 in the prefrontal cortex of rats in each group were observed by immunofluorescence and Western blotting. Results Compared with the control group,sleep deprivation reduced the choice accuracy (<0.001) and increased the omission responses,omission percent,and mean correct response latency (=0.002,=0.003,=0.020).Compared with the sleep deprivation group,medium- and high-dose Schisandrae Chinensis Fructus lignans and atomoxetine hydrochloride improved the alertness of rats,as demonstrated by the increased choice accuracy (=0.001,=0.006,<0.001) and reduced omission responses (=0.001,=0.001,<0.001),omission percent (=0.001,=0.002,<0.001),and mean correct response latency (=0.018,=0.003,=0.014).Compared with the control group,the sleep deprivation group showed elevated level of orexin A in the serum (<0.001),up-regulated expression of c-Fos (<0.001),and down-regulated expression of orexin receptor 1 (=0.037) in the prefrontal cortex.Compared with the sleep deprivation group,Schisandrae Chinensis Fructus lignans (67.2 mg/kg) and atomoxetine hydrochloride lowered the orexin A level in the serum (=0.005,=0.029),down-regulated the expression of c-Fos (=0.028,=0.036),and up-regulated the expression of orexin receptor 1 (=0.043,=0.013) in the prefrontal cortex. Conclusion Schisandrae Chinensis Fructus lignans may antagonize the alertness decrease caused by sleep deprivation by regulating the secretion of orexin and the expression of orexin receptor 1 in the prefrontal cortex.
目的 探讨五味子果实木脂素对跑步机运动致睡眠剥夺大鼠警觉性的影响及其潜在的神经生物学机制。方法 按照随机数字表法，将雄性SD大鼠分为对照组、睡眠剥夺组、低、中、高剂量五味子果实木脂素组和盐酸托莫西汀组，每组8只。除对照组外，其他组大鼠通过跑步机运动进行3 d睡眠剥夺。在剥夺期间，各给药组经灌胃给予相应药物，采用5 - 9孔测试仪检测各组大鼠的警觉性表现。此外，另选雄性SD大鼠，随机分为对照组、睡眠剥夺组、五味子果实木脂素（67.2 mg/kg）组和盐酸托莫西汀组，每组10只。采用与上述相同的睡眠剥夺方法造模并给予相应药物。采用ELISA法检测各组大鼠血清中食欲素A水平。通过免疫荧光和蛋白质印迹法观察各组大鼠前额叶皮质中c - Fos、食欲素受体1和食欲素受体2的蛋白水平。结果 与对照组相比，睡眠剥夺降低了选择准确性（<0.001），增加了漏报反应、漏报百分比和平均正确反应潜伏期（=0.002，=0.003，=0.020）。与睡眠剥夺组相比，中、高剂量五味子果实木脂素和盐酸托莫西汀提高了大鼠的警觉性，表现为选择准确性增加（=0.001，=0.006，<0.001），漏报反应（=0.001，=0.001，<0.001）、漏报百分比（=0.001，=0.002，<0.001）和平均正确反应潜伏期降低（=0.018，=0.003，=0.014）。与对照组相比，睡眠剥夺组血清中食欲素A水平升高（<0.001），前额叶皮质中c - Fos表达上调（<0.001），食欲素受体1表达下调（=0.037）。与睡眠剥夺组相比，五味子果实木脂素（67.2 mg/kg）和盐酸托莫西汀降低了血清中食欲素A水平（=0.005，=0.029），下调了前额叶皮质中c - Fos的表达（=0.028，=0.036），上调了食欲素受体1的表达（=0.043，=0.013）。结论 五味子果实木脂素可能通过调节食欲素的分泌及前额叶皮质中食欲素受体1的表达来拮抗睡眠剥夺所致的警觉性下降。
