大鼠腹外侧视前区P物质对睡眠的影响及其作用机制的研究

The effect and mechanism of substance P in the ventrolateral preoptic area on sleep of rats

目的探讨大鼠下丘脑腹外侧视前区(vLPO)中P物质(SP)对睡眠的影响及其作用机制。方法SD大鼠120只,分实验组(64只)和对照组(16只),40只不符合要求剔除。采用脑立体定位、核团插管、微量注射、多导睡眠描记和免疫组织化学染色等方法观察vLPO中SP对睡眠的影响及其机制。结果大鼠下丘脑vLPO内微量注射SP后与对照组比较睡眠时间增加13.1%,特别是深慢波睡眠,觉醒时间减少22.0%;而在vLPO内微量注射SP受体阻断剂后睡眠时间减少19.6%,觉醒时间增加31.9%。vLPO内微量注射磷脂酶C抑制剂U73122或γ-氨基丁酸(GABA)合成关键酶(谷氨酸脱羧酶)抑制剂3-巯基丙酸均可阻断SP的促眠作用。结论SP在大鼠vLPO中具有促进睡眠,特别是提高深慢波睡眠的作用,该效应可能是通过vLPO中GABA能神经元介导的。

Objective To investigate the effect and mechanism of substance P （SP） in the ventrolateral preoptic area （vLPO） on sleep of rats. Methods Eighty rats were divided into 8 experimental groups and 2 control groups with 8 rats each. Brain stereotaxic technigne, nucleus spile, microinjection, polysomnography and immtmohistochemistry were used to observe effect of SP in vLPO on sleep and its mechanism. Results Sleep was enhanced by 13.1% and wakefulness was reduced by 22.0% after SP was microinjected into bilateral vLPO, while N-acetyl-L-tryptophan 3,5-bis （ trifluoromethyl）-benzyl ester, the SIP receptor （ NK-1 ） antagonist, led to the opposite effects. The effect of SP was blocked by U73122, a phospholipase C inhibitor. In addition, 3-mereaptopropionic acid （3-MP）, a glutamic acid decarboxylase inhibitor that inhibits gamma-aminobutyric acid（ GABA） synthesis and release, blocked the sleep-promoting effect of SP in the vLPO. Conclusion These results indicate that SP in the vLPO can promote sleep, especially deep slow wave sleep and the effect might be mediated by GABAergie neurons of vLPO.