柴桂枣安汤对失眠模型大鼠的治疗作用及其机制

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摘要目的: 研究柴桂枣安汤对对氯苯丙氨酸（p-Chlorophenylalanine，PCPA）所致失眠模型大鼠的治疗作用及机制。方法: 雄性SD大鼠随机分成5组，即正常组、模型组、阳性药组（地西泮1 g/kg）和柴桂枣安汤高（30 g/kg）、低（15 g/kg）剂量组，每组5只。除正常组外，各组腹腔注射350 mg/kg PCPA（1 mL/100 g体重），连续注射3 d。观察大鼠行为，出现昼夜节律消失表明模型制备成功。造模成功后第1天，柴桂枣安汤高、低剂量组，阳性药组，按照1 mL/100 g体重灌胃给药，正常组与模型组给予等体积生理盐水，连续灌胃7 d。观察大鼠自发活动，检测其血清脑源性神经营养因子（BDNF）、Bcl-2、Bax、IL-2、IL-6和胶质纤维酸性蛋白（GFAP）。结果：与正常组相比，模型组活动时间延长且站立次数明显增加（P<0.05）；与给药前相比，给药后柴桂枣安汤高剂量组活动时间明显缩短且站立次数明显减少（P<0.05）。与模型组比较，柴桂枣安汤高剂量组血清中BDNF含量显著升高（P<0.05），柴桂枣安汤高、低剂量组血清中GFAP含量均显著降低（P<0.05），血清IL-2、IL-6、Bcl-2含量及Bcl-2/Bax比值显著升高（P<0.05）。与柴桂枣安汤低剂量组比较，柴桂枣安汤高剂量组血清BDNF、IL-2、Bcl-2含量及Bcl2/Bax比值显著升高，IL-6和GFAP含量显著降低（P<0.05）。结论：柴桂枣安汤可改善失眠，能够缩短PCPA所致失眠模型大鼠的活动时间，减少其站立次数，可能与调节神经保护因子BDNF含量，凋亡相关因子Bcl-2、Bax和细胞因子IL-2、IL-6含量，抑制星形胶质细胞增生、活化有关。

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	胡春艳1
	郭齐1
	刘港1
	刘雪玲1
	查心仪1
	高雨欣1
	周睿晨1
	陆素琴2

关键词 ：柴桂枣安汤, 失眠, 脑源性神经营养因子, 细胞因子, 凋亡相关因子

Abstract：Objective: To evaluate the therapeutic effect and mechanism of Chaiguizaoan Decoction on pChlorophenylalanine（PCPA） induced insomnia model rats. Methods: Male SD rats randomly divided into 5 groups, namely, the normal group, model group, positive drug group （diazepam 1 g/kg）, the Chaiguizaoan Decoction high dose group（30 g/kg） and the low dose group（15 g/kg）, 5 rats in each group. In addition to the normal group, each group was intraperitoneally injected with 350 mg/kg PCPA at 1 mL/100 g, and the normal group was given the same volume of normal saline, which was continuously injected for 3 d.The disappearance of circadian rhythm in rats indicated that the model was successfully prepared. On the first day after the success of the model, the highdose and lowdose Chaiguizaoan Decoction group and the positive group were administered orally at 1 mL/100 g, while the normal group and model group were given normal saline of the same volume for 7 d continuously.The spontaneous activity of rats was observed, and serum brain-derived neurotrophic factor（BDNF）, Bcl2, Bax, IL2, IL6 and glial fibrillary acidic protein（GFAP） indexes were detected. Results: Compared with the normal group, the activity time and standing times of the rats in the model group were significantly increased （P<0.05）. Compared with before administroation, the activity time and standing times of the insomnia model rats were significantly shortened in Chaiguizaoan highdose group（P<0.05）. Compared with model group, serum BDNF content in Chaiguizaoan Decoction highdose group was significantly increased （P<0.05）.Serum GFAP content of Chaiguizaoan Decoction in high- and low-dose groups was remarkably decreased （P<0.05）, serum IL-2, IL-6, Bcl-2 content and Bcl-2/Bax ratio were significantly increased（P<0.05）.Compared with Chaiguizaoan Decoction highdose group, serum BDNF, IL2, Bcl-2 content and Bcl-2/Bax ratio were greatly increased, while IL-6 and GFAP content was markedly decreased （P<0.05）. Conclusion: Chaiguizaoan Decoction could attenuate insomnia, shorten the activity time and reduce the standing times of insomnia model rats induced by PCPA, which may be attributed to regulating the content of neuroprotective factor BDNF, apoptosisrelated factors Bcl-2 and Bax, cytokines IL-2 and IL-6, and inhibiting the proliferation and activation of astrocytes.

收稿日期: 2020-10-22

基金资助: 国家自然科学基金资助项目（81803991）；国家中医临床研究基地（江苏省中医院）开放课题（JD2019SZ16）；江苏省中医药科技发展计划项目重点项目（ZD201911）；镇江市社会发展项目（SH2018046，SH2018053，SH2019042）；2019年度镇江市169人才科研项目；2020年江苏省及江苏大学大学生实践创新训练计划项目

通讯作者: 陆素琴（通讯作者），教授，主任中医师，E-mail：suqin0511@126.com

作者简介: 胡春艳（1998—），女，硕士研究生

引用本文:

胡春艳1，郭齐1，刘港1，刘雪玲1，查心仪1，高雨欣1，周睿晨1，陆素琴2. 柴桂枣安汤对失眠模型大鼠的治疗作用及其机制[J]. 江苏大学学报:医学版, 2021, 31(02): 147-151. HU Chunyan1, GUO Qi1, LIU Gang1, LIU Xueling1, ZHA Xinyi1, GAO Yuxin1, ZHOU Ruichen1, LU Suqin2.

Effect of Chaiguizaoan Decoction on insomnia rat model and its potential mechanism

. Journal of Jiangsu University(Medicine Edition), 2021, 31(02): 147-151.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2021/V31/I02/147

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