外侧下丘脑与褪黑素降低大鼠觉醒水平的关系及受体机制

Relationship between lateral hypothalamus and melatonin-induced reduction of wakefulness in rats and the receptor mechanism

目的探讨外侧下丘脑与褪黑素降低大鼠觉醒水平的关系及受体机制。方法清洁级成年雄性SD大鼠40只,体重250~300 g,采用随机数字表法将大鼠分为4组(n=10):对照组(C组)外侧下丘脑区微注射0.9%NaCl溶液0.5μl;褪黑素组(M组)外侧下丘脑区微注射1μmol/L褪黑素0.5μl;1/2型褪黑素受体(MT1/2R)拮抗剂+褪黑素组(L+M组)外侧下丘脑区微注射1μmol/L MT1/2R拮抗剂和1μmol/L褪黑素,共0.5μl;2型褪黑素受体(MT2R)拮抗剂+褪黑素组(P+M组)外侧下丘脑区微注射1μmol/L MT2R拮抗剂和1μmol/L褪黑素,共0.5μl。微注射给药时间为19:30至20:00,微注射给药后通过脑电/肌电记录技术,检测小鼠睡眠-觉醒时长与脑电不同频段振荡能量。结果与C组比较,M组和P+M组觉醒时间百分比减少,非快速眼动睡眠以及快速眼动睡眠时间百分比增加,delta振荡能量增加,theta振荡能量减少(P<0.01),alpha振荡能量差异无统学意义,L+M组上述指标比较差异无统计学意义(P>0.05)。与M组比较,L+M组觉醒时间百分比增加,非快速眼动睡眠以及快速眼动睡眠时间百分比减少,delta振荡能量减少,theta振荡能量增加(P<0.01),P+M组上述指标差异无统计学意义(P>0.05)。结论外侧下丘脑可能参与了褪黑素诱发的大鼠觉醒水平降低,机制可能与褪黑素激活外侧下丘脑MT1R有关。

Objective To investigate the relationship between lateral hypothalamus and melatonin-induced reduction of wakefulness in rats and the receptor mechanism.Methods Forty clean-grade adult male Sprague-Dawley rats,weighing 250-300 g,were divided into 4 groups(n=10 each)using a random number table method:control group(group C),melatonin group(group M),melatonin type-1/2 receptor(MT1R)antagonist luzindole plus melatonin group(group L+M),and melatonin type-2 receptor(MT2R)antagonist 4P-PDOT plus melatonin group(P+M group).In group C,0.5μl of 0.9%NaCl solution was microinjected into the lateral hypothalamus.In group M,1μmol/L melatonin 0.5μl was microinjected into the lateral hypothalamus.In group L+M,1μmol/L MT1/2R and 1μmol/L melatonin(0.5μl in total)was microinjected into the lateral hypothalamus.The microinjection time was from 19:30 to 20:00.The changes in sleep-wake duration and the oscillating energy in different frequency bands of electroencephalogram were detected by using electroencephalogram and electromyogram recording technology.Results Compared with group C,the percentage of wakefulness time was significantly decreased,the percentage of non-rapid eye movement sleep and rapid eye movement sleep time was increased,the energy for delta oscillation was increased,the energy for theta oscillation was decreased,and no significant change was found in the energy for alpha oscillation in M and P+M groups(P<0.01),and no significant change was found in the parameters mentioned above in group L+M(P>0.05).Compared with group M,the percentage of wakefulness time was significantly increased,the percentage of non-rapid eye movement sleep and rapid eye movement sleep time was decreased,the energy for delta oscillation was decreased,and the energy for theta oscillation was increased in group L+M(P<0.01),and no significant change was found in the parameters mentioned above in group P+M(P>0.05).Conclusion The lateral hypothalamus may be involved in melatonin-induced reduction of wakefulness in rats,and the mechanism may be related to activating MT1R in the lateral hypothalamus.