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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
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王旭艳 ,王鑫鑫 ,冯振宇 ,孟 霜 ,马小娟 ,赵 杰 ,赵建平 (1.山西中医药大学中药与食品工程学院,
1*
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山西 晋中 030619;2.山西省中西医结合医院中心实验室,太原 030013)
中图分类号 R965;R285.5 文献标志码 A 文章编号 1001-0408(2023)06-0671-07
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(P<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(P<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(P<0.05或P<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。
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
Effects of Wenyang jieyu decoction on PI3K/Akt signaling pathway and neurotransmitters in kidney-yang
deficiency depressed rats
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WANG Xuyan ,WANG Xinxin ,FENG Zhenyu ,MENG Shuang ,MA Xiaojuan ,ZHAO Jie ,ZHAO Jianping 1
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(1. College of Chinese Medicine and Food Engineering, Shanxi University of Chinese Medicine,Shanxi Jinzhong
030619, China; 2. Central Laboratory, Shanxi Hospital of Integrated Traditional Chinese and Western Medicine,
Taiyuan 030013, China)
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
Δ 基金项目 山 西 省 基 础 研 究 计 划 青 年 科 学 研 究 项 目(No.
rate, indexes of adrenal gland, thymus gland and spleen,
20210302124565);山西省卫生健康委员会重点实验室建设计划项目;
山西省重点实验室项目(No.202104010910011) serum levels of cyclic adenosine phosphate (cAMP), brain-
*第一作者 硕士研究生。研究方向:中药临床应用。电话:0351- derived neurotrophic factor and gamma-aminobutyric acid, the
2150899。E-mail:1196133050@qq.com
ratio of cAMP to cyclic guanosine monophosphate, the
# 通信作者 主任药师,博士生导师。研究方向:临床中药学、中药
药理学。电话:0351-2150899。E-mail:4668719@163.com contents of norepinephrine, dopamine and 5-hydroxy-
中国药房 2023年第34卷第6期 China Pharmacy 2023 Vol. 34 No. 6 · 671 ·