范恩宇;魏振华;范秋领;郝淑娟;

• 1:杭州娃哈哈集团有限公司浙江省食品生物工程重点实验室

摘要(Abstract)：

本研究探讨了黑柄炭角菌菌核乌灵菌粉的改善睡眠作用以及对小鼠大脑神经递质及其受体的影响。144例小鼠随机分为低、中、高3个剂量(0.25、0.5和1.0 g/kg bw)的乌灵菌粉实验组和1个空白对照组，进行了30 d的灌胃干预，从小鼠睡眠行为和其大脑组织中神经递质及其受体两个方面进行分析。结果显示，乌灵菌粉无直接催眠作用，对小鼠正常生长和体重增长无显著影响。相比于对照组，乌灵菌粉3个剂量实验组巴比妥钠诱导的入睡潜伏期均显著缩短(P<0.05)，戊巴比妥钠阈下剂量下入睡动物数均有增加，戊巴比妥钠诱导的睡眠时间仅有中、高两个剂量组显著增加(P<0.05)，低剂量组睡眠时间增加不显著(P>0.05)。低、中、高3个剂量组小鼠大脑组织中γ-氨基丁酸A型受体(GABA_AR)表达量均显著上升(P<0.05),γ-氨基丁酸B型受体(GABA_BR)表达量却显著下降(P<0.05),5-羟色胺(5-HT)和γ-氨基丁酸含量均显著上升(P<0.01)。综上所述，乌灵菌粉具有明显的改善睡眠功效，其作用机制可能是通过提高脑中5-HT和GABA含量，促进小鼠大脑组织中GABA_AR受体表达来实现。

关键词(KeyWords)： 失眠;睡眠行为;γ-氨基丁酸A型受体;γ-氨基丁酸B型受体;5-羟色胺

Abstract:

Keywords:

基金项目(Foundation):

作者(Authors): 范恩宇;魏振华;范秋领;郝淑娟;

DOI: 10.13346/j.mycosystema.210491

参考文献(References)：

• Alessi C,Vitiello MV,2011.Insomnia(primary) in older people.Clinical Evidence,10:2302
• Chen YH,Zhang B,Huang W,Liu N,Cao SJ,Yang WM,2021.Clinical efficacy of wuling capsule combined with eszopiclone in treatment of insomnia with disharmony between heart and kindey.Journal of Anhui Traditional Chinese Medical College,40(1):18-21 (in Chinese)
• Dai Y,Zhu XQ,Wu LG,2018.Study on sedative and hypnotic effective part of wuling mycelia.Journal of Chende Medical College,35(4):342-344 (in Chinese)
• Dai YC,Yang ZL,2008.A revised checklist of medicinal fungi in China.Mycosystema,27:801-824 (in Chinese)
• Li FL,Du F,Wu D,Peng ZW,2016.Effects of early usage with wulingjun powder on the behavior of rats with post-traumatic stress disorder and the level of IL-1βand IL-6 in their hippocampi.China Pharmacy,27(25):3478-3480 (in Chinese)
• Li Y,2018.Clinical observation on jiaotai pill and wuling capsule in the treatment of insomnia due to heart-kidney dissymmetry.Cardiovascular Disease Journal of Integrated Traditional Chinese and Western Medicine,6(35):151-152 (in Chinese)
• Liao ML,Yu J,2000.Wuling capsule.Chinese New Drugs Journal,9(11):797 (in Chinese)
• Liu XM,Zhang R,Dong SF,Cheng GN,Chang HS,Sun JN,2016.Effects of mixture of wuling powder and Hypericum perforatum L.on depressed model rats induced by chronic unpredictable stress.Chinese Journal of Comparative Medicine,26(5):81-86 (in Chinese)
• Liu XY,2018.Study on the clinical efficacy safety of wuling capsule in the treatment of insomnia.Master Thesis,Hubei University of Chinese Medicine,Wuhan.1-33(in Chinese)
• Luo W,Peng XG,Ye XD,Fang MC,Cheng M,Miao YP,Chen AY,Dong WB,Zheng GL,2019.Research on radioprotective activity of wuling bacteria fermentation bulk.Chinese Journal of Modern Applied Pharmacy,36(6):675-681 (in Chinese)
• Ma SY,Li T,Wei MQ,Ni JN,Xu XQ,Wang X,Yao X,Zhou YY,Shi J,2022.The efficacy and safety of wuling capsule in treatment of sleep disorder:a meta analysis.World Chinese Medicine,17(5):715-722 (in Chinese)
• Ma ZZ,Zuo PP,Chen WR,Tang LJ,Shen Q,Sun XH,Shen Y,1999.Studies on the sedative and sleeping effects of wuling mycelia and its pharmacological mechanism.Chinese Pharmaceutical Journal,34(6):374-377(in Chinese)
• Nowicki Z,Grabowski K,Cuba?a JW,Nowicka-Sauer K,Zdrojewski T,Rutkowski M,Bandosz P,2016.Prevalence of self-reported insomnia in general population of Poland.Psychiatria Polska,50(1):165-173
• Qiu T,Chen M,Tao SL,Dai JF,Wu LC,Zhang BH,2007.Effect of wuling powder on the changes of hippocampal monoamine neurotransmitter and behaviors in post-stroke depression rats.Chinese Journal of New Drugs,16(11):857-860 (in Chinese)
• Sun LJ,Han QY,Hu M,2016.Research progress onγ-aminobutyric acid(GABA) receptors.Heilongjiang Animal Science and Veterinary Medicine,4:80-83(in Chinese)
• Tang NN,Wu CW,Chen MQ,Zeng XA,Wang XF,Zhang Y,Huang JS,2017.Therapeutic effects of jiaotai pill on rat insomnia via regulation of GABA signal pathway.Tropical Journal of Pharmaceutical Research,16(9):2135-2140
• Wang J,Hu YL,2021.Clinical study on wuling capsules for insomnia of heart-kidney non-interaction type.Journal of New Chinese Medicine,53(12):71-74 (in Chinese)
• Wang YM,Chen HG,Song M,Xu SJ,Yu LL,Wang L,Wang R,Shi L,He J,Huang YQ,Sun HQ,Pan CY,Wang XY,Lu L,2016.Prevalence of insomnia and its risk factors in older individuals:a community-based study in four cities of Hebei Province,China.Sleep Medicine,19:116-122
• Wen SF,Cao Y,Yang LL,Zhou ZF,Li RC,2019.Research progress on medicinal Xylaria.Edible and Medicinal Mushrooms,27(2):106-111 (in Chinese)
• Wu F,Zhou LW,Yang ZL,Bau T,Li TH,Dai YC,2019.Resource diversity of Chinese macrofungi:edible,medicinal and poisonous species.Fungal Diversity,98:1-76
• Wu XF,Zheng XN,Guo X,Xie ZQ,Xie LN,Yue ZH,2018.Effects of acupuncture treatment on 5-HT,its receptors and HPA-related hormones in rats with insomnia.Chinese Archives of Traditional Chinese Medicine,36(1):127-129 (in Chinese)
• Yan Y,Li Q,Du HZ,Shen CX,Li AP,Pei XP,Du CH,Qin XM,2019.Determination of five neurotransmitters in the rat brain for the study of the hypnotic effects of ziziphi spinosae semen aqueous extract on insomnia rat model by UPLC-MS/MS.Chinese Journal of Natural Medicines,17(7):551-560
• Yang N,Liu YY,Hao WY,Ji C,Mou L,Zuo PP,2010.Anti-depressant mechanisms of wulingjun powder by gene microarray analysis.Chinese Journal of Rehabilitation Theory and Practice,16(4):328-331(in Chinese)
• Yin DH,Zhang J,Liu CL,2011.Advance in clinical application of wuling capsule.Chinese Journal of New Drugs,20(16):1530-1533 (in Chinese)
• You WJ,He WD,Ma SH,Ling QZ,2021.Research progress on neuromodulation of wuling powder.Science and Technology&Innovation,7(4):14-17 (in Chinese)
• Zhang L,Yang YF,Zhu JP,Hu JQ,2020.Advance in pharmcology,clinical application of wuling preparation.Chinese Traditional Patent Medicine,42(12):3241-3245(in Chinese)
• 陈永华，张波，黄为，刘妮，曹仕健，杨文明，2021.乌灵胶囊联合右佐匹克隆治疗心肾不交型失眠临床观察.安徽中医药大学学报，40(1):18-21
• 戴一，朱向群，吴灵刚，2018.乌灵参镇静催眠有效部位研究.承德医学院学报，35(4):342-344
• 戴玉成，杨祝良，2008.中国药用真菌名录及部分名称的修订.菌物学报，27:801-824
• 李凤蕾，杜菲，吴迪，彭正午，2016.乌灵菌粉早期应用对创伤后应激障碍模型大鼠行为及海马组织中IL-1β、IL-6水平的影响.中国药房，27(25):3478-3480
• 李鹰，2018.交泰丸加减联合乌灵胶囊治疗心肾不交失眠的疗效观察.中西医结合心血管病杂志，6(35):151-152
• 廖名龙，郁杰，2000.乌灵胶囊.中国新药杂志，9(11):797
• 刘晓萌，张荣，董世芬，程工倪，畅洪昇，孙建宁，2016.乌灵菌粉贯叶连翘复方制剂干预对慢性不可预知应激大鼠模型抗抑郁作用及机制的研究.中国比较医学杂质，26(5):81-86
• 刘晓燕，2018.乌灵胶囊治疗失眠的临床疗效及安全性研究.湖北中医药大学硕士论文，武汉.1-33
• 罗威，彭晓国，叶小弟，方明春，程敏，缪云萍，陈爱瑛，董文彬，郑高利，2019.乌灵菌发酵液抗辐射功能研究.中国现代应用药学，36(6):675-681
• 马素亚，李婷，魏明清，倪敬年，徐筱青，王旭，姚璇，周英奕，时晶，2022.乌灵胶囊治疗睡眠障碍有效性及安全性Meta分析.世界中医药，17(5):715-722
• 马志章，左萍萍，陈宛如，唐利军，沈琦，孙晓华，沈云，1999.乌灵菌粉的镇静作用及其机理研究.中国药学杂志，34(6):374-377
• 裘涛，陈眉，陶水良，代建峰，吴乐程，张宾辉，2007.乌灵菌粉对脑卒中后抑郁大鼠海马区单胺类神经递质及行为学改变的影响.中国新药杂志，16(11):857-860
• 孙利净，韩秋月，胡满，2016.γ-氨基丁酸(GABA)受体的研究进展.黑龙江畜牧兽医，4:80-83
• 王静，胡艳丽，2021.乌灵胶囊治疗心肾不交型失眠临床研究.新中医，53(12):71-74
• 闻绍锋，曹瑶，杨林雷，周忠发，李荣春，2019.药用炭角菌的研究进展.食药用菌，27(2):106-111
• 吴雪芬，郑雪娜，郭鑫，谢志强，谢莉娜，岳增辉，2018.针刺对失眠大鼠5-HT及其受体、HPA轴相关激素影响的研究进展.中华中医药学刊，36(1):127-129
• 杨楠，刘雁勇，郝文宇，纪超，牟亮，左萍萍，2010.应用基因芯片技术探讨乌灵菌粉的抗抑郁机制.中国康复理论与实践，16(4):328-331
• 尹东辉，张晶，刘纯莉，2011.乌灵胶囊的临床应用进展.中国新药杂志，20(16):1530-1533
• 尤伟静，何文迪，马少华，凌庆枝，2021.乌灵菌粉神经调节作用机制研究进展.科技与创新，7(4):14-17
• 张丽，杨耀芳，朱建萍，胡坚强，2020.乌灵菌制剂药理作用、临床应用的研究进展.中成药，42(12):3241-3245