人参醇提取物对老年果蝇睡眠的改善作用及其机制

人参醇提取物对老年果蝇睡眠的改善作用及其机制

Improvement effect of ginseng alcohol extract on sleep of aged drosophila and its mechanism

摘要/Abstract

图/表 9

参考文献 28

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吉林大学学报(医学版)

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刘建¹,邢鹭²,兰天野³,姚璠⁴,王雯⁵,董玉福¹,吴金普¹,毕然¹,孙立伟²,陈雪楠²(),赵为民⁴()

^1.长春中医药大学中医学院，吉林长春 130117
^2.长春中医药大学附属医院实验中心，吉林长春 130022
^3.长春中医药大学附属医院康复科，吉林长春 130022
^4.长春中医药大学附属医院治未病科，吉林长春 130022
^5.长春中医药大学信息管理学院，吉林长春 130117

收稿日期:2024-09-05 接受日期:2024-10-28
通讯作者: 陈雪楠,赵为民 E-mail:chenxiaobao0310@126.com;zwm630123@126.com
作者简介:刘建（1994-），男，吉林省长春市人，在读博士研究生，主要从事睡眠障碍基础与临床方面的研究。
基金资助:
国家自然科学基金区域创新发展联合基金项目(U20A20402);吉林省科技厅科技发展计划项目(YDZJ202301ZYTS463);吉林省中医药管理局中医药科技项目(2024044);吉林省教育厅科学技术研究项目(JJKH20230972KJ)

Jian LIU¹,Lu XING²,Tianye LAN³,Fan YAO⁴,Wen WANG⁵,Yufu DONG¹,Jinpu WU¹,Ran BI¹,Liwei SUN²,Xuenan CHEN²(),Weimin ZHAO⁴()

^1.College of Traditional Chinese Medicine，Changchun University of Chinese Medicine，Changchun 130117，China
^2.Experimental Center，Affiliated Hospital，Changchun University of Chinese Medicine，Changchun 130022，China
^3.Department of Rehabilitation，Affiliated Hospital，Changchun University of Chinese Medicine，Changchun 130022，China
^4.Department of Preventive Medicine，Affiliated Hospital，Changchun University of Chinese Medicine，Changchun 130022，China
^5.College of Information Management，Changchun University of Chinese Medicine，Changchun 130117，China

Received:2024-09-05 Accepted:2024-10-28
Contact: Xuenan CHEN,Weimin ZHAO E-mail:chenxiaobao0310@126.com;zwm630123@126.com

摘要：

目的探讨人参醇提取物（GEE）通过维持氧化还原平衡改善老年果蝇模型睡眠的作用，并阐明其相关作用机制。方法随机选取32只7 d龄雄性黑腹果蝇作为年轻组，另选64只35 d龄雄性黑腹果蝇随机分为老年组和GEE组，每组32只。培养基给药7 d后利用DAM2果蝇行为学分析系统分析各组果蝇总睡眠时长、日间睡眠时长、夜间睡眠时长、关灯后4 h内睡眠时长（ZT0-4睡眠时长）、深睡眠时长、睡眠发生次数和睡眠片段化等睡眠参数以及总自主活动次数、日间自主活动次数和夜间自主活动量等活动参数。利用基于双向荧光差异凝胶电泳（2D-DIGE）和基质辅助激光解析电离飞行时间质谱（MALDI-TOF-MS）的蛋白质组学方法对果蝇脑组织中差异表达蛋白进行筛选、鉴定及功能分析。利用试剂盒法检测各组果蝇脑组织中超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px）活性及脂质过氧化产物（MDA）水平。结果与年轻组比较，老年组果蝇总睡眠时长、日间睡眠时长和夜间睡眠时长缩短（P<0.05或P<0.01）；与老年组比较，GEE组果蝇总睡眠时长、日间睡眠时长和夜间睡眠时长明显延长（P<0.01）。与年轻组比较，老年组果蝇ZT0-4睡眠时长、深睡眠时长和睡眠片段化缩短（P<0.05或P<0.01），睡眠节律振幅缩短；与老年组比较，GEE组果蝇ZT0-4睡眠时长、深睡眠时长和睡眠片段化延长（P<0.01），睡眠节律振幅提高。2D-DIGE电泳图谱中共筛选出47个差异表达蛋白，与年轻组比较，老年组表达下调；与老年组比较，GEE组蛋白表达上调，差异表达蛋白主要包括谷胱甘肽S转移酶、过氧化物氧还蛋白1和二氢硫辛酸脱氢酶等调控氧化还原平衡相关的蛋白。与年轻组比较，老年组果蝇脑组织中SOD、CAT和GSH-Px活性降低（P<0.05或P<0.01），MDA水平升高（P<0.01）；与老年组比较，GEE组果蝇脑组织中SOD、CAT和GSH-Px活性升高（P<0.05或P<0.01），MDA水平降低（P<0.05）。结论 GEE对老年果蝇睡眠具有改善作用，其机制可能与提高抗氧化酶活性、抑制MDA积累和维持氧化还原平衡有关。

关键词: 人参, 老年, 睡眠, 氧化还原平衡, 黑腹果蝇, 蛋白质组

Abstract:

Objective To investigate the impact of ginseng alcohol extract （GEE） on improving sleep quality in the aged Drosophila model by regulating the redox balance， and to elucidate its associated mechanism. Methods Thirty-two male drosophila melanogaster （7-days-old） were randomly selected as young group， while 64 male Drosophila melanogaster flies （35-days-old） were randomly assigned to aged model group and GEE group. The sleep parameters， including total sleep duration， daytime sleep duration， night sleep duration， 0-4 h of sleep duration after lights off （ZT0-4 sleep duration）， deep sleep duration， sleep episodetimes， sleep fragmentation， and the activity parameters such as the total number of locomotor activity daytime locomotor activity amount and nighttime locomotor activity amount were analyzed using the DAM2 Drosophila behavioral analysis system 7 d after medium administration. The differentially expressed proteins in drosophila brain tissue were screened， identified， and functionally analyzed using two-dimensional fluorescence difference gel electrophoresis（2D-DIGE） and matrix-assisted laser desorption/ionization time of flight mass spectrometry（MALDI-TOF/TOF-MS） proteomic methods. The activities of superoxide dismutase （SOD）， catalase （CAT）， and glutathione peroxidase （GSH-Px） and the levels of lipid peroxidation product （MDA） in brain tissue of the drosophila were determined using assay kits. Results Compared with young group， the total sleep duration daytime sleep duration and night sleep cluration of the drosophila in agaed group were decreased（P<0.01 or P<0.05）； and the sleep rhythm amplitude was shortened. Compared with aged group， the total sleep duration and daytime and nighttime sleep durations of the drosphila in GEE group were lengthened （P<0.01）. Compared with young group， the ZT0-4 sleep duration deep sleep duration and sleep fragment of the drosophila in aged group were decreased （P<0.01 or P<0.05）， and the sleep rhythm amplitude was shortened. Compared with young group， the ZT0-4 sleep duration， deep sleep duration， and single sleep fragment of the drosphila in GEE group were significantly prolonged （P<0.01）， and the sleep amplitude was increased. A total of 47 differentially expressed proteins were selected in the 2D-DIGE electrophoretic mapping. Compared with young group， the expressions of 47 differentially expressed protein sites in aged group were down-regulated mainly including glutathione S-transferase， peroxiredoxin 1 and dihydrolipoic dehydrogenase， which were related to redox balance. Compared with young group， the activities of SOD， CAT and GSH-Px in brain tissue of the drosophila in aged group were decreased （P<0.05 or P<0.01）， and the level of MDA was increased （P<0.01）； compared with aged group， the activities of SOD， CAT and GSH-Px in brain tissue of the drosphila in GEE group were increased （P<0.05 or P<0.01）， and the MDA level was decreased （P<0.05）. Conclusion GEE has improvement effect on the sleep quality of aged drosophila， and its possible mechanism may be related to upregulating the activities of antioxidant enzymes， inhibiting the accumulation of lipid peroxidation products， and maintaining redox balance.

Key words: Ginseng, Aging, Sleep, Redox balance, Drosophila melanogaster, Proteome

中图分类号:

R285.5

刘建,邢鹭,兰天野,姚璠,王雯,董玉福,吴金普,毕然,孙立伟,陈雪楠,赵为民. 人参醇提取物对老年果蝇睡眠的改善作用及其机制[J]. 吉林大学学报(医学版), 2025, (): 1-8.

Jian LIU,Lu XING,Tianye LAN,Fan YAO,Wen WANG,Yufu DONG,Jinpu WU,Ran BI,Liwei SUN,Xuenan CHEN,Weimin ZHAO. Improvement effect of ginseng alcohol extract on sleep of aged drosophila and its mechanism[J]. Journal of Jilin University(Medicine Edition), 2025, (): 1-8.

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Group	Daytime sleep duration	Nighttime sleep duration	Total sleep duration
Young	267.66±170.11	487.34±155.82	755.00±217.28
Aged	162.81±133.84^*	385.94±169.35^*	548.75±203.37^**
GEE	367.50±125.19^△	568.13±88.59^△	935.63±176.53^△

Group	ZT0-4 sleep time	Deep sleep time
Young	164.38±45.20	267.66±170.11
Aged	129.38±64.34^*	162.81±133.84^*
GEE	174.84±40.48^△	367.50±125.19^△

Group	Sleep episode times (time·24 h^-1)	Sleep fragmentation (t/min)
Young	28.41±8.34	30.87±13.82
Aged	27.41±10.20^*	17.26±8.59^*
GEE	25.47±8.99^△	39.52±18.64^△

Group	Daytime locomotor activity	Nighttime locomotor activity	Total number of locomotor activity	Single activity duration (t/min)
Young	518.25±300.74	320.66±266.87	838.91±512.36	38.15±30.75
Aged	696.75±354.32	416.97±252.08^*	1 113.72±570.12	38.30±19.56
GEE	488.50±346.46^△	204.50±145.92^△△	693.00±436.15^△△	31.60±21.07

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