Effect of Wenyang Jieyu Decoction on Hippocampal Neuroplasticity in Depressed Rats Induced by Corticosterone

Xin-xin WANG; Jie ZHAO; Zhen-yu FENG; Xiao-juan MA; Shuang MENG; Min SHI; Xiao-rong ZHOU; Jian-ping ZHAO

doi:10.13422/j.cnki.syfjx.20220237

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Effect of Wenyang Jieyu Decoction on Hippocampal Neuroplasticity in Depressed Rats Induced by Corticosterone

更新时间：2021-12-14

- Effect of Wenyang Jieyu Decoction on Hippocampal Neuroplasticity in Depressed Rats Induced by Corticosterone
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 28, Issue 2, Pages: 93-103(2022)
- 作者机构：
  
  1.山西中医药大学，太原 030619
  2.山西省中西医结合医院，太原 030013
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20220237
  CLC： R2-0;R33;R289;R246.6
- Published：20 January 2022，
  
  Published Online：20 November 2021，
  
  Received：10 August 2021，
- 稿件说明：
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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(02):93-103.

WANG Xin-xin,ZHAO Jie,FENG Zhen-yu,et al.Effect of Wenyang Jieyu Decoction on Hippocampal Neuroplasticity in Depressed Rats Induced by Corticosterone[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(02):93-103.
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(02):93-103. DOI： 10.13422/j.cnki.syfjx.20220237.

WANG Xin-xin,ZHAO Jie,FENG Zhen-yu,et al.Effect of Wenyang Jieyu Decoction on Hippocampal Neuroplasticity in Depressed Rats Induced by Corticosterone[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(02):93-103. DOI： 10.13422/j.cnki.syfjx.20220237.

摘要

目的

通过建立肾阳虚型抑郁症大鼠模型，观察温阳解郁汤对大鼠海马组织结构的干预作用。

方法

将105只SD大鼠随机分为正常组，模型组，氟西汀组（4.17 mg·kg

-1

），逍遥散组（1.88 g·kg

-1

）及温阳解郁汤低、中、高剂量组（1.25，2.50，5.00 g·kg

-1

），每组15只，除正常组外其他各组采用皮下注射皮质酮诱导抑郁症大鼠模型，造模同时灌胃给药，每天1次，连续28 d。通过糖水偏好实验、新环境进食抑制实验、强迫游泳实验、旷场实验反应大鼠的抑郁状态。苏木素-伊红（HE）染色观察海马神经元形态，尼氏染色检测海马区神经元细胞密度，透射电镜观察海马突触超微结构，免疫组化观察海马神经元突触前标志性蛋白突触小泡蛋白（SYP），突触后标志性蛋白95（PSD95）及凋亡相关蛋白半胱氨酸天冬氨酸蛋白水解酶-3（Caspase-3）的表达，免疫荧光双标新生神经细胞的标记物溴脱氧核苷尿嘧啶（BrdU），微管相关蛋白（DCX）观察海马神经元凋亡、再生情况。

结果

温阳解郁汤可改善抑郁大鼠体质量降低的现象，通过行为学检测发现模型组大鼠出现抑郁行为，温阳解郁汤及氟西汀组大鼠抑郁行为得到改善。HE染色结果显示，模型组大鼠海马神经元细胞核固缩、深染，排列稀疏，温阳解郁汤及氟西汀组大鼠神经元细胞明显改善。尼氏染色结果显示，与正常组比较，模型组大鼠细胞密度明显降低（

0.05）；与模型组比较，温阳解郁汤组、氟西汀组及逍遥散组大鼠细胞密度明显增加（

0.05），排列紧凑。电镜结果显示，与正常组比较，模型组大鼠突触活性带长度明显缩短（

0.05），突触间隙明显增宽（

0.05），致密区厚度明显变薄（

0.05）；与模型组比较，温阳解郁汤组、氟西汀组及逍遥散组大鼠突触活性带长度明显变短（

0.05），突触间隙明显缩小（

0.05），致密区厚度明显增厚（

0.05）。免疫组化及免疫荧光结果显示，与正常组比较，模型组大鼠海马组织SYP，PSD95，BrdU，DCX的蛋白表达明显降低（

0.05），Caspase-3蛋白表达明显增加（

0.05）；与模型组比较，温阳解郁汤组、氟西汀组及逍遥散组大鼠海马组织SYP，PSD95，BrdU，DCX蛋白表达明显增加（

0.05），Caspase-3蛋白表达明显降低（

0.05）。

结论

温阳解郁汤能够促进大鼠海马神经元再生，改善抑郁大鼠抑郁状态。

Abstract

Objective

To observe the effect of Wenyang Jieyu decoction （WYJY） on the hippocampal structure of depressed rats with kidney-yang deficiency.

Method

The 105 SD rats were randomly divided into normal group， model group， fluoxetine group （4.17 mg·kg

-1

）， Xiaoyaosan group （1.88 g·kg

-1

）， and low-， medium- and high-dose （1.25，2.50，5.00 g·kg

-1

） WYJY groups，15 in each group. The depression model was induced by subcutaneous injection of corticosterone in rats except for those in the normal group and the rats were orally administered once a day for 28 days. The depression-like behaviors of rats were observed by sucrose preference test， novelty-suppressed feeding test， forced swimming test， and open field test. The morphology of hippocampal neurons was observed by hematoxylin-eosin（HE） staining， and the density of hippocampal neurons was detected by Nissl staining. The ultrastructure of hippocampal synapses was observed by transmission electron microscopy （TEM）. The expression of synaptophysin （SYP）， postsynaptic density-95 （PSD95）， and apoptosis-related protein Caspase-3 in hippocampal neurons was observed by immunohistochemistry， and bromodeoxyuridine （BrdU） and doublecortin （DCX） were used to observe the apoptosis and regeneration of hippocampal neurons.

Result

WYJY could improve weight loss in depressed rats. As revealed by the behavioral tests， the model group showed depression-like behaviors， which were relieved in the WYJY groups and the positive drug groups. HE staining showed that the nuclei of hippocampal neurons in the model group were constricted， deeply stained， and sparsely arranged， while the neurons in the WYJY groups and the positive drug groups were significantly improved. Nissl staining demonstrated that the cell density of the model group was lower than that of the normal group （

0.05）. Compared with model group， the groups with drug intervention showed increased cell density （

0.05） and compact arrangement. According to the results in TEM， compared with normal group， the model group showed shortened synaptic active zone （

0.05）， widened synaptic cleft （

0.05）， and thinned tight zone （

0.05）. Compared with model group， the groups with drug intervention showed shortened synaptic active zone （

0.05）， narrowed synaptic cleft （

0.05）， and thickened tight zone （

0.05）. As displayed by the results of immunocytochemistry and immunofluorescence， compared with the normal group， the model group showed decreased protein expression of SYP， PSD95， BrdU， and DCX in the hippocampus （

0.05） and increased protein expression of Caspase-3 （

0.05）. Compared with the model group， the groups with drug intervention showed increased protein expression of SYP， PSD95， BrdU， and DCX in the hippocampus （

0.05） and decreased protein expression of Caspase-3 （

0.05）.

Conclusion

WYJY can promote the regeneration of hippocampal neurons in rats and improve the depression of rats.

关键词

温阳解郁汤抑郁症海马神经可塑性突触超微结构

Keywords

Wenyang Jieyu decoctiondepressionhippocampal neuroplasticitysynapseultrastructure

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