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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
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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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                                           2
          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 ·
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