Effects of Wenyang jieyu decoction on PI3K/Akt signaling pathway and neurotransmitters in kidney-yang deficiency depressed rats

WANG Xuyan; WANG Xinxin; FENG Zhenyu; MENG Shuang; MA Xiaojuan; ZHAO Jie; ZHAO Jianping

doi:10.6039/j.issn.1001-0408.2023.06.06

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Effects of Wenyang jieyu decoction on PI3K/Akt signaling pathway and neurotransmitters in kidney-yang deficiency depressed rats

更新时间：2023-03-24

- Effects of Wenyang jieyu decoction on PI3K/Akt signaling pathway and neurotransmitters in kidney-yang deficiency depressed rats
- ZHONGGUO YAOFANG Vol. 34, Issue 6, Pages: 671-677(2023)
- 作者机构：
  
  1.山西中医药大学中药与食品工程学院，山西晋中　030619
  2.山西省中西医结合医院中心实验室，太原　030013
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.06.06
  CLC： R965;R285.5
- Published：30 March 2023，
  
  Received：09 August 2022，
  
  Revised：31 January 2023，
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王旭艳,王鑫鑫,冯振宇等.温阳解郁汤对肾阳虚型抑郁大鼠PI3K/Akt信号通路及神经递质的影响 ^Δ[J].中国药房,2023,34(06):671-677.

WANG Xuyan,WANG Xinxin,FENG Zhenyu,et al.Effects of Wenyang jieyu decoction on PI3K/Akt signaling pathway and neurotransmitters in kidney-yang deficiency depressed rats[J].ZHONGGUO YAOFANG,2023,34(06):671-677.
王旭艳,王鑫鑫,冯振宇等.温阳解郁汤对肾阳虚型抑郁大鼠PI3K/Akt信号通路及神经递质的影响 ^Δ[J].中国药房,2023,34(06):671-677. DOI： 10.6039/j.issn.1001-0408.2023.06.06.

WANG Xuyan,WANG Xinxin,FENG Zhenyu,et al.Effects of Wenyang jieyu decoction on PI3K/Akt signaling pathway and neurotransmitters in kidney-yang deficiency depressed rats[J].ZHONGGUO YAOFANG,2023,34(06):671-677. DOI： 10.6039/j.issn.1001-0408.2023.06.06.

摘要

目的

探讨温阳解郁汤对肾阳虚抑郁症大鼠磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）信号通路及神经递质的影响。

方法

将雄性SD大鼠分为空白组、模型组、氟西汀组（西药阳性对照，4.17 mg/kg）、逍遥散组（中药阳性对照，1.88 g/kg）和温阳解郁汤低、中、高剂量组（1.25、2.50、5.00 g/kg），每组15只。除空白组外，其余各组均皮下注射皮质酮20 mg/kg以复制肾阳虚型抑郁大鼠模型，并同时灌胃相应药液，每天1次，连续28 d。观察大鼠的一般情况，检测其糖水偏好率、强迫游泳静止不动时间，计算其脏器指数，检测其血清中神经递质水平/含量，检测其海马组织中PI3K/Akt通路相关蛋白的表达量和树突棘数量。

结果

与空白组比较，模型组大鼠出现了掉毛、畏冷扎堆、蜷缩等症状，糖水偏好率，肾上腺、胸腺、脾指数，血清环磷酸腺苷（cAMP）、脑源性神经营养因子、γ氨基丁酸水平，cAMP与环磷酸鸟苷比值，去甲肾上腺素、多巴胺、5-羟色胺含量，PI3K、Akt、哺乳动物雷帕霉素靶蛋白的表达量，以及海马组织中树突棘数量均显著降低（

＜0.01）；静止不动时间、谷氨酸水平、糖原合成酶激酶3β蛋白的表达量均显著延长或升高（

＜0.01）。与模型组比较，各药物组大鼠的抑郁症状有所改善，上述指标大部分逆转（

＜0.05或

＜0.01）。

结论

温阳解郁汤可改善大鼠的抑郁样行为和肾阳虚状态，调节神经递质的分泌，并可激活PI3K/Akt信号通路，从而起到保护海马神经元的作用。

Abstract

OBJECTIVE

To investigate the effects of Wenyang jieyu decoction on phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway and neurotransmitters in rats with kidney-yang deficiency depression.

METHODS

The SD rats were divided into blank group， model group， fluoxetine group （positive control of western medicine， 4.17 mg/kg）， Xiaoyao powder group （positive control of TCM， 1.88 g/kg） and Wenyang jieyu decoction low-dose， medium-dose and high-dose groups （1.25， 2.50， 5.00 g/kg）， with 15 rats in each group. Except for blank group， the other groups were treated with corticosterone 20 mg/kg subcutaneously to induce kidney-yang deficiency depressed model， meanwhile the mice were given relevant medicine intragastrically， once a day， for 28 consecutive days. The general conditions of rats were observed. The sucrose preference rate and the static time of forced swimming were detected， and organ indexes of rats were calculated. The levels/contents of neurotransmitters in serum were detected， the expressions of PI3K/Akt pathway-related proteins in hippocampus were detected， and the number of dendritic spines was determined.

RESULTS

Compared with blank group， model group suffered from the symptoms such as hair loss， fear of cold， curling up； sucrose preference rate， indexes of adrenal gland， thymus gland and spleen， serum levels of cyclic adenosine phosphate （cAMP）， brain-derived neurotrophic factor and gamma-aminobutyric acid， the ratio of cAMP to cyclic guanosine monophosphate， the contents of norepinephrine， dopamine and 5-hydroxy-tryptamine， the expressions of PI3K， Akt， mammalian target of rapamycin， and the number of dendritic spines in the hippocampus were significantly decreased （

＜0.01）. The time of immobility， level of glutamic acid and protein expression of glycogen synthetase kinase-3β were prolonged and increased （

＜0.01）. Compared with model group， depression symptoms of rats in each administration group were improved， and the above indexes were mostly reversed （

＜0.05 or

＜0.01）.

CONCLUSIONS

Wenyang jieyu decoction can improve depression-like behavior and the deficiency of kidney-yang， regulate the secretion of neurotransmitters， and activate PI3K/Akt signaling pathway， thus playing a role in protecting hippocampal neurons.

关键词

温阳解郁汤抑郁症肾阳虚磷脂酰肌醇3激酶/蛋白激酶B信号通路神经递质大鼠

Keywords

depressionkidney-yang deficiencyPI3K/Akt signaling pathwayneurotransmitterrat

references

马凌悦，向倩，周颖，等. 心境障碍及其治疗与生物节律相关性的研究现状[J]. 中国临床药理学杂志，2019，35（14）：1533-1536.

DEY A，HANKEY GIBLIN P A. Insights into macrophage heterogeneity and cytokine-induced neuroinflam-mation in major depressive disorder[J]. Pharmaceuticals（Basel），2018，11（3）：64.

MICHALIS G，BELLOS S，POLITIS S，et al. Epidemi- ology of alcohol use in late adolescence in Greece and comorbidity with depression and other common mental disorders[J]. Depress Res Treat，2019，2019：5871857.

徐宁阳，任路，杨关林. 基于“脑-心-肾”轴理论构建冠心病合并抑郁症的中医防治体系[J]. 中华中医药杂志，2022，37（5）：2677-2680.

赵杰，彭涛，马艳苗. 温阳解郁汤治疗抑郁症30例临床观察[J]. 山西中医，2011，27（7）：15-16.

冯振宇，赵杰，刘慧宇. 温阳解郁汤对抑郁模型大鼠HPA轴的影响[J]. 中华中医药杂志，2015，30（12）：4304-4307.

王鑫鑫，赵杰，冯振宇，等. 温阳解郁汤对皮质酮诱导的抑郁大鼠海马神经可塑性的影响[J]. 中国实验方剂学杂志，2022，28（2）：93-103.

唐维我，张会永，李芹，等. 肾阳虚证动物模型造模方法及模型评价[J]. 世界科学技术-中医药现代化，2021，23（4）：1317-1324.

孟霜，冯振宇，马小娟，等. 温阳解郁颗粒对抑郁模型大鼠行为学和血清中单胺类神经递质水平的影响[J]. 中国药房，2019，30（23）：3226-3231.

GREGUS A，WINTINK A J，DAVIS A C，et al. Effect of repeated corticosterone injections and restraint stress on anxiety and depression-like behavior in male rats[J]. Behav Brain Res，2005，156（1）：105-114.

PIZZAGALLI D A. Depression，stress，and anhedonia：toward a synthesis and integrated model[J]. Annu Rev Clin Psychol，2014，10：393-423.

STREKALOVA T，SPANAGEL R，BARTSCH D，et al. Stress-induced anhedonia in mice is associated with deficits in forced swimming and exploration[J]. Neuropsychopharmacology，2004，29（11）：2007-2017.

严林，欧则民，王艳静，等. 泽泻及其炮制品对肾阴虚水肿模型大鼠的作用机制[J]. 中国实验方剂学杂志，2022，28（24）：42-49.

ZALETEL I，FILIPOVIĆ D，PUŠKAŠ N. Hippocampal BDNF in physiological conditions and social isolation[J]. Rev Neurosci，2017，28（6）：675-692.

尹传红，闫宇辉. 高压氧通过激活CREB/BDNF信号通路减轻阿尔茨海默病小鼠海马神经元突触损伤[J]. 中国病理生理杂志，2020，36（6）：1063-1070.

BAK L K，SCHOUSBOE A，WAAGEPETERSEN H S. The glutamate/GABA-glutamine cycle：aspects of tran-sport，neurotransmitter homeostasis and ammonia transfer[J]. J Neurochem，2006，98（3）：641-653.

KITAMURA A，TSURUGIZAWA T，UEMATSU A，et al. New therapeutic strategy for amino acid medicine：effects of dietary glutamate on gut and brain function[J]. J Pharmacol Sci，2012，118（2）：138-144.

刘晓，洪浩. 谷氨酸-谷氨酰胺循环在抑郁症发病机制中作用的研究进展[J]. 今日药学，2022，32（3）：206-210.

赵洪庆，韩远山，柳卓，等. 焦虑性抑郁模型大鼠脑区单胺递质含量与神经因子表达的变化[J]. 中国实验动物学报，2017，25（4）：373-379.

尚立芝，毛梦迪，许二平，等. 柴胡加龙骨牡蛎汤对抑郁大鼠海马组织PI3K/Akt/GSK3β/β-catenin信号通路的影响[J]. 中国实验方剂学杂志，2020，26（23）：12-19.

杨茜，王静，裴双义. 文拉法辛对抑郁模型大鼠认知功能及海马神经元凋亡的作用研究[J]. 中国免疫学杂志，2018，34（11）：1642-1648.

张治楠，梁丽艳，连嘉惠，等. 中枢神经系统PI3K/AKT/mTOR信号通路研究进展[J]. 实用医学杂志，2020，36（5）：689-694.

IGNÁCIO Z M，RÉUS G Z，ARENT C O，et al. New per-spectives on the involvement of mTOR in depression as well as in the action of antidepressant drugs[J]. Br J Clin Pharmacol，2016，82（5）：1280-1290.

凌志峰，罗洪斌，谢枫枫，等. 柴胡越鞠汤对CUMS诱导的抑郁症模型大鼠治疗作用及其机制[J]. 中国实验方剂学杂志，2020，26（21）：68-76.

SHRESTHA B R，VITOLO O V，JOSHI P，et al. Amyloid beta peptide adversely affects spine number and motility in hippocampal neurons[J]. Mol Cell Neurosci，2006，33（3）：274-282.

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