姜黄素对睡眠剥夺小鼠认知功能的改善作用及其机制

doi:10.13481/j.1671-587x.20190630

摘要/Abstract

摘要： 目的：研究姜黄素对睡眠剥夺小鼠认知功能和海马组织中Toll样受体4/核转录因子κB （TLR4/NF-κB）通路的影响，探讨姜黄素治疗睡眠剥夺的机制。方法：将100只小鼠随机分为对照组，模型组，低、中和高剂量姜黄素组，每组20只。除对照组外，其他各组小鼠采用改良多平台水环境睡眠剥夺法建立睡眠剥夺模型；建模后，低、中和高剂量姜黄素组小鼠分别腹腔注射5、10及20 mg·kg^-1姜黄素，每天1次，共3 d。Morris水迷宫实验测定各组小鼠学习记忆能力，旷场实验测定小鼠垂直得分和水平得分，ELISA法检测各组小鼠海马组织中白细胞介素1β（IL-1β）和白细胞介素6（IL-6）水平，Western blotting法检测各组小鼠海马组织中TLR4和NF-κB p65蛋白表达水平，RT-PCR法检测各组小鼠海马组织中IL-1β、IL-6、TLR4和NF-κB mRNA表达水平。结果：与模型组比较，各剂量姜黄素组小鼠逃避潜伏期缩短（P<0.05），停留原平台象限时间延长（P<0.05），穿越原平台次数增加（P<0.05），旷场实验垂直得分和水平得分降低（P<0.05），小鼠海马组织中IL-1β、IL-6、TLR4和NF-κB P65蛋白表达水平均降低（P<0.05），小鼠海马组织中IL-1β、IL-6、TLR4和NF-κB mRNA表达水平降低（P<0.05），且呈剂量依赖性。结论：姜黄素可能通过抑制TLR4/NF-κB通路改善睡眠剥夺小鼠的认知功能。

关键词: 姜黄素, 睡眠剥夺, 认知功能, 海马, Toll样受体4, 核转录因子κB, 白细胞介素1β, 白细胞介素6

Abstract: Objective: To study the effects of curcumin on the cognitive function and Toll-like receptor 4/nuclear transcription factor-κB (TLR4/NF-κB) pathway in hippocampus tissue of the mice with sleep deprivation, and to explore the mechanism of curcumin in the treatment of sleep deprivation. Methods: A total of 100 mice were randomly divided into control group, model group and low,middle, high doses of curcumin groups,and there were 20 mice in each group.Except control group,the mice in the other groups were established sleep deprivation models by modified multi-platform water environment sleep deprivation method;after modeling, the mice in low, meddle and high doses of curcumin groups were intraperitoneally injected with 5, 10, and 20 mg·kg^-1 curcumin, once a day for 3 d. Morris water maze test was used to determine the learning and memory abilities of the mice in various groups,and open-field test was used to determine the rearing and crossing scores of the mice in various groups; the levels of interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the hippocampus tissue of the mice in various groups were detected by ELISA method, the expression levels of TLR4 and NF-κB p65 proteins in hippocampus tissue of the mice in various groups were detected by Western blotting method, and the expression levels of IL-1β, IL-6, TLR4, and NF-κB mRNA in hippocampus tissue of the mice in various groups were detected by RT-PCR method. Results: Compared with model group, the escape latencies of the mice in different doses of curcumin groups were shortened (P<0.05), the time of staying on the original platform quadrant was prolonged(P<0.05), the times of crossing the original platform were increased (P<0.05), the rearing and crossing scores of the mice in open-field test were decreased (P<0.05),the expression levels of IL-1β, IL-6, TLR4 and NF-κB p56 proteins in hippocampus tissue of the mice in various groups were significantly decreased (P<0.05),and the expression levels of IL-1β, IL-6, TLR4 and NF-κB mRNA in hippocampus tissue of the mice in various groups were decreased(P<0.05). Conclusion: Curcumin may improve the cognitive function in the mice with sleep deprivation by inhibiting the TLR4/NF-κB pathway.

Key words: curcumin, sleep deprivation, cognitive function, hippocampus, Toll-like receptor 4, nuclear transcription factor-κB, interleukin-1β, interleukin-6

中图分类号:

R256.23

赵翠, 王淼, 张颖, 冯玉梅, 曹亚文, 蒋海森, 李伟. 姜黄素对睡眠剥夺小鼠认知功能的改善作用及其机制[J]. 吉林大学学报(医学版), 2019, 45(06): 1373-1378.

ZHAO Miao, WANG Yi, ZHANG Ying, FENG Yumei, CAO Yawen, JIANG Haisen, LI Wei. Improvement effect of curcumin on cognitive function in mice with sleep deprivation and its mechanism[J]. Journal of Jilin University(Medicine Edition), 2019, 45(06): 1373-1378.

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