目的 探究姜黄素对密闭环境条件下小鼠睡眠障碍的干预作用。方法 将36只昆明雄性小鼠随机分为对照组（CON组）、模型组（M组）、姜黄素组（J组）。CON组在动物房常规条件下饲养;M组和J组在生物节律箱设定光照条件下施加束缚4 h,光照条件为：前3 d与CON组光照时间相反,第4 d至第6 d与CON组光照时间相同,6d为一个循环,J组每日灌胃100 mg/ (kg·bw)姜黄素,CON组、M组给予等量生理盐水。小鼠干预30 d后实验结束,采用腹腔注射戊巴比妥钠进行小鼠诱导睡眠实验,记录睡眠潜伏期及睡眠时间;处死后取血清及下丘脑组织,酶联免疫吸附法（ELISA）测定小鼠血清中的皮质醇（CORT）、促肾上皮质激素释放激素（CRH）、促肾上腺皮质激素（ACTH）以及下丘脑组织中的5-羟色胺（5-HT）、多巴胺（DA）等指标,并用RT-qPCR检测下丘脑相关时钟基因表达。结果 在戊巴比妥钠诱导小鼠睡眠试验中,姜黄素可显著缩短睡眠潜伏期（P<0.01）,延长睡眠时间（P<0.01）。血清相关激素含量测定结果表明,与M组相比,姜黄素可显著降低CORT、ACTH、CRH含量（P<0.01,P<0.05）。在下丘脑相关神经递质含量测定中,与M组相比,J组5-HT含量显著增加（P<0.01）,DA含量显著降低（P<0.05）。与M组相比,姜黄素具有调节生物节律基因（Clock、Bmal1、Per1、Per2、Per3、Cry1、Cry2、Rev-erbα/β）基因表达振幅的作用。结论 姜黄素可能通过影响相关生物节律基因表达,调节血清相关激素及神经递质水平,使其趋于恢复,从而发挥改善睡眠障碍的作用。
Abstract
Objective To investigate the effect of curcumin on sleep disorder in mice exposed to confined environmental conditions. Methods Thirty-six male KM mice were randomly assigned to the control group (CON), model group (M), and curcumin group (J). The CON group was kept under the usual conditions in the animal house. The M group and J group were restrained for 4h in a biorhythm box under the altered light condition. The light condition in one cycle was as follows: the light time was opposite to that of the CON group in the first 3d, and returned to the normal from the 4th to the 6th. Group J was given 100 mg/ (kg·bw) curcumin by gavage daily, group con and M was given an equal amount of saline.The experiment lasted for 30 d. The mice were injected intraperitoneally with sodium pentobarbital to induce sleep, and the sleep latency and duration were recorded. Finally mice were sacrificed and the serum and hypothalamus tissues were taken. The contents of cortisol (CORT), corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) in serum and 5-hydroxytryptamine (5-HT) and dopamine (DA) in hypothalamus tissues were measured by enzyme-linked immunosorbent assay (ELISA). The expressions of hypothalamus-associated clock genes were detected by RT-qPCR. Results The results of the sodium pentobarbital-induced sleep test showed that curcumin significantly shortened sleep latency (P<0.01) and prolonged sleep time (P<0.01). Meanwhile curcumin significantly reduced serum CORT, ACTH, and CRH levels compared with the group M (P<0.01, P<0.05). In the hypothalamus-related neurotransmitters, 5-HT content was significantly increased (P<0.01) and DA content was significantly decreased (P < 0.05) in group J compared with group M. Curcumin could regulate the expressions of biorhythmic genes (Clock, Bmal1, Per1, Per2, Per3, Cry1, Cry2, Rev-erbα/β) in the hypothalamus. Conclusion Curcumin improves sleep disorder by modulating the expression of related biorhythmic genes and altering related serum hormones and hypothalamic neurotransmitters.
关键词
密闭环境 /
睡眠障碍 /
姜黄素 /
下丘脑神经递质 /
血清激素 /
生物节律基因
Key words
confined environment /
sleep disorder /
curcumin /
hypothalamic neurotransmitters /
serum hormone /
biological rhythm genes
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基金
国家自然科学基金（No. 81903307）
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