姜黄素通过调节自噬改善睡眠剥夺小鼠认知功能及抑郁样行为的作用

职业与健康 ›› 2025, Vol. 41 ›› Issue (2): 177-180.

姜黄素通过调节自噬改善睡眠剥夺小鼠认知功能及抑郁样行为的作用

孙婷婷¹, 王琮民², 董静³, 单铁强¹, 宋亚娟⁴, 祁皎¹

1.秦皇岛市海港医院检验科,河北秦皇岛 066000;
2.河北工程大学医学院,河北邯郸056002;
3.邯郸市疾病预防控制中心检验科,河北邯郸 056002;
4.邯郸市中心医院检验科,河北邯郸 056002

收稿日期:2024-01-17 修回日期:2024-02-07 出版日期:2025-01-15 发布日期:2025-12-11
通信作者: 董静,副主任技师,E-mail：zxw071009@163.com
作者简介:孙婷婷,女,主管检验师,主要从事临床检验工作。

Effect of curcuminon improving cognitive function and depressive like behavior in sleep deprived mice by regulating autophagy

SUN Tingting¹, WANG Congmin², DONG Jing², SHAN Tieqiang¹, SONG Yajuan⁴, QI Jiao¹

1. Laboratory Department, Qinhuangdao Haigang Hospital, Qinhuangdao, Hebei 066000, China;
2. School of Medicine, Hebei University of Engineering, Handan, Hebei 056002, China;
3. Laboratory Department, Handan Center for Disease Control and Prevention, Handan, Hebei 056002, China;
4. Laboratory Department, Handan Central Hospital, Handan, Hebei 056002, China

Received:2024-01-17 Revised:2024-02-07 Online:2025-01-15 Published:2025-12-11
Contact: DONG Jing,Deputy chief technician,E-mail：zxw071009@163.com

摘要/Abstract

摘要： 目的分析姜黄素对睡眠剥夺小鼠学习记忆能力、抑郁样行为及海马组织内自噬蛋白、磷脂酰肌醇3 激酶（phosphatidylinositol 3-kinase,PI3K）/丝苏氨酸激酶（serine kinase,AKT）通路蛋白的影响,探讨姜黄素拮抗睡眠剥夺诱导的认知功能及抑郁样行为的作用机制。方法通过“改良平台水环境”法制备剥夺睡眠小鼠模型,实验分为正常对照组、睡眠剥夺组及姜黄素组。姜黄素组腹腔分别注射姜黄素10和20 mg/kg,正常对照组和睡眠剥夺组腹腔注射等体积的0.9%氯化钠。每日1次,持续7 天。水迷宫实验测量各组小鼠的认知功能;敞箱实验、糖水偏好实验评估各组小鼠的抑郁样行为;蛋白印迹法分析海马组织内自噬蛋白：Bcl-2同源结构域蛋白抗体（Beclin 1）、微管相关蛋白轻链3II（LC3II）/微管相关蛋白轻链3I（LC3I）的含量,磷酸化磷酸肌醇3激酶（p-PI3K）/PI3K、磷酸化丝苏氨酸激酶（p-AKT）/AKT的含量。结果与正常对照组比较,睡眠剥夺小鼠逃避潜伏期[（43.79±6.17）s]延长,穿越平台数[（10.48±1.28）次]减少（均P<0.01）;穿越格子数（53.27±7.99）、直立次数（45.63±6.56）、糖水偏好率[（32.61±4.97）%]均降低（均P<0.01）;海马组织内Beclin 1（1.58±0.16）、 LC3II/LC3I（1.21±0.16）水平均上升（均P<0.01）,p-PI3K/PI3K（0.26±0.03）及p-AKT/AKT（0.40±0.05）水平均下降（均P<0.01）。与睡眠剥夺组比较,姜黄素组逃避潜伏期[（31.89±3.81、27.01±3.41）s]缩短,穿越平台数[（16.57±1.90、20.26±2.55）次]增加（均P<0.01）;穿越格子数（95.39±13.88、114.76±14.94）、直立次数（74.32±7.99、86.25±9.42）、糖水偏好率[（43.09±5.46、51.89±7.38）%]均升高（均P<0.01）;海马组织内Beclin 1（1.07±0.11、0.92±0.10）、 LC3II/LC3I（0.89±0.11、0.72±0.11）水平均下降（均P<0.01）,p-PI3K/PI3K（0.51±0.06、0.61±0.06）及p-AKT/AKT（0.59±0.06、0.68±0.07）水平均上升（均P<0.01）,且呈剂量依赖性。结论姜黄素能提高睡眠剥夺小鼠的认知功能并减轻抑郁样行为,这与其激活PI3K/AKT通路抑制海马组织自噬密切相关。

关键词: 姜黄素, 睡眠剥夺, 认知功能, 抑郁样行为, 自噬, PI3K/AKT通路

Abstract: Objective To analyze the effects of curcumin on learning and memory ability,depressive like behavior,and autophagy proteins,phosphatidylinositol 3 kinase（PI3K）/serine kinase（AKT） pathway proteins in hippocampal tissue in sleep deprived mice,and to explore the mechanism of curcumin antagonizing cognitive function and depressive like behavior induced by sleep deprivation. Methods A sleep deprived mouse model was prepared using the "improved platform water environment" method,and the experiment was arranged into a normal control group,a sleep deprivation group and a curcumin group. The curcumin group were injected intraperitoneally with 10 and 20 mg/kg curcumin,respectively,while the normal control group and sleep deprivation group were injected intraperitoneally with an equal volume of 0.9% sodium chloride. Once daily for 7 days. The water maze experiment was used to measure the cognitive function of mice in each group. The open box experiment and sugar water preference experiment were used to evaluate the depression like behavior of mice in each group. Western blotting was used to analyze the content of autophagic proteins Bcl-2 homologous domain protein antibody（Beclin 1）,microtubule associated protein light chain 3II（LC3II）/microtubule associated protein light chain 3I（LC3I） in hippocampal tissue,as well as the content of phosphorylated phosphoinositol 3-kinase（p-PI3K）/PI3K and phosphorylated serine kinase（p-AKT）/AKT autophagic proteins. Results Compared with the normal control group,the escape latency[（43.79±6.17）s] of sleep deprived mice was prolonged,and the number of crossing platforms[（10.48±1.28）times] was reduced（both P<0.01）,the number of crossing score（53.27±7.99）,the number of crossing score（45.63±6.56）,and the preference rate for sugar water[（32.61±4.97）%] all decreased（all P<0.01）,the levels of Beclin 1（1.58±0.16） and LC3II/LC3I （1.21±0.16） in hippocampal tissue increased（both P<0.01）,while the levels of p-PI3K/PI3K（0.26±0.03） and p-AKT/AKT（0.40±0.05） decreased（both P<0.01）. Compared with the sleep deprivation group,the curcumin group had a shorter escape latency[（31.89±3.81,27.01±3.41）s] and an increased number of crossing platforms[（16.57±1.90,20.26±2.55）times]（all P<0.01）,the number of crossing score（95.39±13.88,114.76±14.94）,rearing score（74.32±7.99, 86.25±9.42） and preference rate for sugar water[（43.09±5.46,51.89±7.38）%] all increased（all P<0.01）,the levels of Beclin 1（1.07±0.11,0.92±0.10） and LC3II/LC3I（0.89±0.11,0.72±0.11） in hippocampal tissue decreased（all P<0.01）,while the levels of p-PI3K/PI3K（0.51±0.06,0.61±0.06） and p-AKT/AKT（0.59±0.06,0.68±0.07） increased（all P<0.01）,and showed a dose-dependent relationship. Conclusion Curcumin can improve cognitive function and alleviate depressive like behavior in sleep deprived mice,which is closely related to its activation of the PI3K/AKT pathway and inhibition of hippocampal autophagy.

Key words: Curcumin, Sleep deprivation, Cognitive function, Depression like behavior, Autophagy, PI3K/AKT pathway

中图分类号:

R-332

孙婷婷, 王琮民, 董静, 单铁强, 宋亚娟, 祁皎. 姜黄素通过调节自噬改善睡眠剥夺小鼠认知功能及抑郁样行为的作用. [J]职业与健康, 2025, 41(2): 177-180.

SUN Tingting, WANG Congmin, DONG Jing, SHAN Tieqiang, SONG Yajuan, QI Jiao. Effect of curcuminon improving cognitive function and depressive like behavior in sleep deprived mice by regulating autophagy. [J]OCCUPATION AND HEALTH, 2025, 41(2): 177-180.

参考文献

[1] 孙毅红,刘心朗,周丽丽,等.睡眠障碍发病机制及对神经退行性病变的影响[J].中国老年学杂志,2022,42(7):1763-1766.
[2] 张晓洋,李笑,吴方,等.失眠对认知功能的影响研究进展[J].新乡医学院学报,2022,39(3):285-288.
[3] 陈春华,陈继华,黄琼,等.睡眠剥夺介导神经元自噬抑制对小鼠抑郁样行为和认知功能的影响[J].东南大学学报(医学版),2021,40(5):657-665.
[4] 游明灿,陈新旺,游言文,等.电针对睡眠剥夺模型大鼠学习记忆能力和Beclin1、LC3B、PI3K及Akt的影响[J].中国中医基础医学杂志,2022,28(12):1969-1974,2022.
[5] 王海英,张宇琪,孙昊天,等.姜黄素及其衍生物的作用及机制[J].生理科学进展,2022,53(4):271-275.
[6] 王耀宇,张雨萌,吕天翼,等.姜黄素的药理作用及其在脑血管疾病与痴呆防治中的研究进展[J].中华老年心脑血管病杂志,2022,24(6):667-669.
[7] 魏丹丹,李玉洁,王永杰,等.圣愈汤通过调节海马区单胺类神经递质水平改善睡眠剥夺小鼠学习、记忆能力[J].中国实验方剂学杂志,2021,27(7):1-8.
[8] 李敬强,王庆福,张璐,等.不同睡眠类型选择性注意在睡眠剥夺中内稳态与昼夜节律研究[J].生物医学工程学杂志,2022,39(2):248-256.
[9] 雷雨,刘伟,王鹏.小檗碱通过NF-κB/iNOS-COX-2信号通路对睡眠剥夺大鼠认知功能的影响[J].中国老年学杂志,2024,44(2):459-462.
[10] 赵翠,王淼,张颖,等.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(6):1373-1378.
[11] 李云,周明眉,苟小军,等.姜黄素对间歇性睡眠剥夺大鼠特定肠道菌的影响[J].中草药,2016,47(5):794-798.
[12] KOMATSU M,WAGURI S,CHIBA T,et al.Loss of autophagy in the central nervous system causes neurodegeneration in mice[J].Nature,2006,441(7095):880-884.
[13] 方永奇,刘林.神经细胞自噬的研究进展[J].中华中医药学刊,2011,29(3):453-455.
[14] CAO Y,LI Q,ZHOU A,et al.Corrigendum:Notoginsenoside R1 Reverses Abnormal Autophagy in Hippocampal Neurons of Mice With Sleep Deprivation Through Melatonin Receptor 1A[J].Front Pharmaco,2022,12:832126.
[15] DAI W,XIAO Y,TU Y,et al.Propofol protects hippocampal neurons in sleep-deprived rats by inhibiting mitophagy and autophagy[J].Ann Transl Med.2021,9(18):1427.
[16] 张磊,赵永强,刘公哲,等.非小细胞肺癌患者组织中自噬相关蛋白Beclin1、LC3、P62的表达水平及临床意义[J].临床和实验医学杂志,2023,22(19):2054-2057.
[17] TRAN S,FAIRLIREWD,LEE E F.BECLIN1:Protein Structure,Function and Regulation[J].Cells,2021,10(6):1522.
[18] PRERNA K,DUBEY V K.Beclin1-mediated interplay between autophagy and apoptosis:New understanding[J].Int J Biol Macromol,2022
204:258-273.
[19] KUMA A,MATSUI M,MIZUSHIMA N.LC3,an autophagosome marker,can be incorporated into protein aggregates independent of autophagy:caution in the interpretation of LC3 localization[J].Autophagy,2007,3(4):323-328.
[20] JI Y,XIONG L,ZHANG G,et al.Synovial fluid exosome-derived miR-182-5p alleviates osteoarthritis by downregulating TNFAIP8 and promoting autophagy through LC3 signaling[J].Int Immunopharmacol,2023,125(Pt A):111177.
[21] 李想,李安特,孙秋霞,等.PI3K/AKt信号通路与神经损伤修复的研究进展[J].中国老年学杂志,2023,43(1):246-249.
[22] KMA L,BARUAH T J.The interplay of ROS and the PI3K/Akt pathway in autophagy regulation[J].Biotechnol Appl Biochem,2022,69(1):248-264.
[23] MA L,ZHANG R,LI D,et al.Fluoride regulates chondrocyte proliferation and autophagy via PI3K/AKT/mTOR signaling pathway[J].Chem Biol Interact,2021,349:109659.
[24] CAO Y,LI Q,ZHOU A,et al.Notoginsenoside R1 reverses abnormal autophagy in hippocampal neurons of mice with sleep deprivation through melatonin receptor 1A[J].Front Pharmacol,2021,12:832126.
[25] GAO S,TANG Y Y,JIANG L,et al.H2S attenuates sleep deprivation-induced cognitive impairment by reducing excessive autophagy via hippocampal Sirt-1 in wistar rats[J].Neurochem Res,2021,46(8):1941-1952.
[26] CAO Y,YANG Y,WU H,et al.Stem-leaf saponins from Panax notoginseng counteract aberrant autophagy and apoptosis in hippocampal neurons of mice with cognitive impairment induced by sleep deprivation[J].J Ginseng Res,2020,44(3):442-452.