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目的:探讨睡眠剥夺(sleep deprivation,SD)对大鼠下丘脑组蛋白乙酰化水平的影响,并观察乙酰化修饰是否影响神经元下丘脑促觉醒肽Orexin A的表达。方法:成年雄性大鼠24只,采用改良多平台睡眠剥夺法建立大鼠SD模型,随机分为对照组(n=6)和SD组(n=18);Western Blot法检测大鼠下丘脑组蛋白乙酰化水平的变化;免疫荧光法观察下丘脑Orexin A神经元。结果:与对照组相比,SD后1 d,3 d及6 d,下丘脑组蛋白H3亚基9位赖氨酸(H3K9)、H3K14位点的乙酰化水平明显下降(P<0.05),但三个时间点之间无显著差异(P>0.05)。SD后3 d,下丘脑的Orexin A+神经元数目和对照组相比明显减少(P<0.05),而给予组蛋白去乙酰化酶抑制剂SAHA(25 mg/kg,i.p.)可部分恢复SD减少的Orexin A~+神经元数(P<0.05)。结论:睡眠剥夺可能通过影响大鼠下丘脑组蛋白的乙酰化修饰水平减少神经元Orexin A的表达。
Objective: To investigate the effect of sleep deprivation (SD) on hypothalamic histone acetylation in rats and to observe whether acetylation affects the expression of Orexin A, a hormone of hypothalamus, in neurons. Methods: Twenty-four adult male rats were divided into control group (n = 6) and SD group (n = 18) by modified multi-platform sleep deprivation method. The hypothalamus group The changes of acetylation level of Orexin A neurons in the hypothalamus were observed by immunofluorescence. Results: Compared with the control group, the acetylation levels of H3K9 and H3K14 at histone H3 subunit of hypothalamus were significantly decreased at 1 d, 3 d and 6 d after SD (P <0.05) However, there was no significant difference between the three time points (P> 0.05). At 3 days after SD, the number of Orexin A + neurons in the hypothalamus decreased significantly compared with that in the control group (P <0.05), whereas administration of the histone deacetylase inhibitor SAHA (25 mg / kg, ip) partially reduced SD Of Orexin A ~ + neurons (P <0.05). Conclusion: Sleep deprivation may reduce the expression of Orexin A in neurons by affecting the histone acetylation level of hypothalamus in rats.