五味子木脂素对跑步机睡眠剥夺大鼠警觉性的影响OA北大核心CSTPCDMEDLINE

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 Ac-cording 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 tread-mill exercise for 3 d.During the deprivation period,each administration group was administrated with the corre-sponding 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 im-munofluorescence and Western blotting.Results Compared with the control group,sleep deprivation reduced the choice accuracy(P＜0.001)and increased the omission responses,omission percent,and mean correct re-sponse latency(P=0.002,P=0.003,P=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(P=0.001,P=0.006,P＜0.001)and reduced omission re-sponses(P=0.001,P=0.001,P＜0.001),omission percent(P=0.001,P=0.002,P＜0.001),and mean correct response latency(P=0.018,P=0.003,P=0.014).Compared with the control group,the sleep deprivation group showed elevated level of orexin A in the serum(P＜0.001),up-regulated expression of c-Fos(P＜0.001),and down-regulated expression of orexin receptor 1(P=0.037)in the prefrontal cor-tex.Compared with the sleep deprivation group,Schisandrae Chinensis Fructus lignans(67.2 mg/kg)and atom-oxetine hydrochloride lowered the orexin A level in the serum(P=0.005,P=0.029),down-regulated the ex-pression of c-Fos(P=0.028,P=0.036),and up-regulated the expression of orexin receptor 1(P=0.043,P=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.