依托咪酯经腹外侧视前核γ-氨基丁酸能神经元产生促眠作用  

Etomidate acts onγ-aminobutyric acid neurons in the ventrolateral preoptic nucleus for promoting sleep

作　　者：张敏[1,2] 范坤[1,2] 邵玉峰[1,2] 赵鹏[1,2] 侯一平[1,2] 

机构地区：[1]兰州大学基础医学院 [2]兰州大学甘肃省新药临床研究重点实验室,甘肃兰州730000

出　　处：《兰州大学学报（医学版）》2011年第1期1-5,10,共6页Journal of Lanzhou University（Medical Sciences）

基　　金：国家自然科学基金(30670677;81071076)

摘　　要：目的揭示非巴比妥类麻醉药依托咪酯的促眠作用与作用途径。方法实验动物随机分为腹外侧视前核损毁前+生理盐水组(E1组,n=6)、腹外侧视前核损毁前+依托咪酯组(E2组,n=6)、腹外侧视前核损毁后+生理盐水组(E3组,n=6)和腹外侧视前核损毁后+依托咪酯组(E4组,n=6)4个组。连续记录脑电图与肌电图,解析大鼠腹外侧视前核的γ-氨基丁酸能神经元损毁前、后腹腔注射依托咪酯睡眠觉醒时相的变化和Fos基因在腹外侧视前核的表达变化。结果 E2组产生脑电图慢波活动增加,肌电图活动减弱或消失,12h(20:00-08:00)各时相时间比E1组觉醒减少35.3%(P<0.01);而浅慢波睡眠、深慢波睡眠、异相睡眠分别增加48.2%(P<0.01)、77.7%(P<0.01)和83.3%(P<0.05);Fos基因在腹外侧视前核表达明显增加。E4组的促眠作用消失,与E2组比较觉醒增加68 4%(P<0 01),而浅慢波睡眠、深慢波睡眠、异相睡眠分别减少29.1%(P<0 05)、69 2%(P<0.01)、43.3%(P<0.05);Fos基因在腹外侧视前核表达明显减少。E3组和E4组分别与E1组相比仅深慢波睡眠分别减少44.1%(P<0.01)、45.3%(P<0.01);但E3组和E4组相比各时相时间无显著变化。E2组和E4组Fos基因表达的阳性神经元数目与深慢波睡眠变化量分析结果为线性关系。结论依托咪酯经腹外侧视前核的γ-氨基丁酸能神经元通路产生促眠作用。Objective To investigate the effect and potential targets of etomidate, a nonbarbi- turate anesthetic, on sleep regulation. Methods Animals are randomly divided into the vehicle group （E1, n=6）, the etomidate group before lesion （E2, n=6）, vehicle group after lesion （E3, n=6）, and etomidate group after lesion （E4, n=6）. The methods of polysomnograph for analyzing each state time across sleep-wake cycle and Fos gene expression for determining the acting targets following etomidate administration during dark-period before and after specific cell lesion in the ventrolateral preoptic nucleus of the rat were employed in the present study. Results Etomidate administration in freely move rats induced an increase in light slow wave sleep （48.2%, P 〈0.01）, deep slow wave sleep （77.7%, P 〈0.01）, paradoxical sleep （83.3%, P 〈0.05） time during 12 hours （20：00-08：00）, and the number of Fos-immunoreactive neurons in the ventrolateral preoptic nucleus, and a decrease in wake （35.3%, P 〈0.01） time, compared with the E1 group, respectively. However, the hypnotic effect of etomidate was attenuated after ventrolateral preoptic nucleus lesion, etomidate administration at corresponding time induced a decrease in slow wave sleep, deep slow wave sleep, paradoxical sleep time respectively by 29.1% （P 〈0.05）, 69.2% （P 〈0.01） and 43.3% （P 〈0.05） and the number of Fos-immunoreactive neurons in the ventrolateral preoptic nucleus, and an increase in wake time by 68.4% （P 〈0.01） compared with the E2 group. The E2 and E3 groups after ventrolateral preoptic nucleus lesion were insignificant difference in each state across sleep-wake cycle, but they exclusively reduced deep slow wave sleep time by 44.1% （P 〈0.01） and 45.3% （P 〈0.01） compared with the E1 group, respectively. The number of remaining Fos-immunoreactive neurons in the ventrolateral preoptic nucleus was linearly related to deep slow wave sleep time. Conclusion Etomidate acts on γ-aminobutyric acid ne

关 键 词：腹外侧视前核 依托咪酯 睡眠 Γ-氨基丁酸 损毁 

分 类 号：R322.85[医药卫生—人体解剖和组织胚胎学]