安寐丹对不同周期睡眠剥夺模型大鼠昼夜节律、学习记忆及食欲素的影响

目的:观察安寐丹对3、6、9月龄睡眠剥夺(SD)模型大鼠昼夜节律、学习记忆及食欲素(OX)的影响并探讨其最佳显效周期及可能机制。方法:根据大鼠生长周期,分别选取3、6、9月龄SD大鼠,运用随机数字表分为空白组、模型组、艾司唑仑组(0.09mg·kg-1·d-1)、安寐丹组(9.09g·kg-1·d-1),除空白组外均采用对氯苯丙氨酸(PCPA)腹腔注射叠加多平台水环境剥夺法建立SD模型,空白组、模型组给予等容0.9%氯化钠溶液灌胃,灌胃1周。运用自主活动仪监测大鼠昼夜节律,Morris水迷宫检测其学习记忆,ELISA检测大鼠血清食欲素A(OXA)、食欲素B(OXB)含量,免疫荧光检测下丘脑区OX含量表达。结果:各月龄大鼠造模后昼夜节律紊乱,其活动时间和活动距离均高于空白组(P<0.05,P<0.01);大鼠造模后下丘脑区OX含量较空白组增多,尤以9月龄大鼠OX含量增多较为明显;安寐丹能一定程度改善SD大鼠上平台潜伏期、游泳总路程、穿越站台次数和象限活动时间(P<0.05,P<0.01),且各月龄改善效果有别,但9月龄大鼠安寐丹灌胃后上平台潜伏期、游泳总路程最短(P<0.01);安寐丹能一定程度降低各月龄SD大鼠OXA、OXB含量(P<0.05,P<0.01),但各月龄降低程度有别,且安寐丹组降低9月龄大鼠OX含量较艾司唑仑组明显。结论:安寐丹能改善不同周期SD模型大鼠的昼夜节律紊乱、学习记忆障碍,其机制可能与调节OXA、OXB有关,且初步认为安寐丹对9月龄SD模型大鼠作用效果最佳。

Effects of Anmei Pill on circadian rhythm,learning and memory and Orexin of sleep deprivation rats in different cycles

Objective: To observe the effects of Anmei Pill(AMP) on circadian rhythm, learning and memory and Orexin(OX) in 3,6,9-month-old SD rats, and to explore its optimal effective cycle and possible mechanism. Methods: According to the growth cycle of rats, SD rats aged 3, 6 and 9 months were randomly divided into blank group, model group, Estazolam group(0.09 mg · kg-1 · d-1) and AMP group(9.09 g · kg-1 · d-1). The SD rats were established by intraperitoneal injection of p-chlorophenylalanine(PCPA) combined with multi platform water deprivation method except the blank group. The blank group and model group were given equal volume 0.9% sodium chloride solution by gavage for 1 week. The circadian rhythm of rats was monitored by autonomic activity instrument. Morris water maze was used to detect their learning and memory. The serum levels of Orexin A(OXA) and Orexin B(OXB) were detected by ELISA. The expression of OX in hypothalamus was detected by immunofluorescence. Results: The circadian rhythm of each month old rats was disordered, and the activity time and distance were higher than those of the blank group(P<0.05, P<0.01);the content of OX in hypothalamus was increased than that in blank group after modeling, especially in 9-month-old rats;and could improve the platform latency, total swimming distance, times of crossing platform and quadrant activity time of SD rats to a certain extent(P<0.05, P<0.01). The results showed that AMP could reduce the content of OXA and OXB in SD rats(P<0.05, P<0.01) to some extent, but the degree of decrease in AMP group was lower than that in Estazolam group. Conclusion: AMP can improve the circadian rhythm disorder and learning and memory disorder of SD model rats in different periods, and its mechanism may be related to the regulation of OXA and OXB, and it is preliminarily considered that AMP has the best effect on 9-month-old SD model rats.