Exploring Mechanism of Chaihu Jia Longgu Mulitang in Depressive-like Rats via AMPK/SIRT1/NF-<italic style="font-style: italic">κ</italic>B/NLRP3 Signaling Pathway

WANG Guang; SONG Xinhua; YANG Jie; XU Jinyao; MEI Junhua; CHEN Chao; CHEN Guohua

doi:10.13422/j.cnki.syfjx.20260167

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Exploring Mechanism of Chaihu Jia Longgu Mulitang in Depressive-like Rats via AMPK/SIRT1/NF-κB/NLRP3 Signaling Pathway

更新时间：2026-04-30

- Exploring Mechanism of Chaihu Jia Longgu Mulitang in Depressive-like Rats via AMPK/SIRT1/NF-κB/NLRP3 Signaling Pathway
  增强出版
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 32, Issue 11, Pages: 144-152(2026)
- 作者机构：
  
  1.湖北中医药大学中医临床学院，武汉 430065
  2.湖北省中医院，武汉 430061
  3.武汉市第八医院，武汉 430010
  4.武汉市第一医院，武汉 430022
  5.武汉市第六医院，武汉 430019
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20260167
  CLC： R242;R971;R277.7
- Received：18 November 2025，
  
  Revised：2026-01-14，
  
  Accepted：10 February 2026，
  
  Online First：11 February 2026，
  
  Published：05 June 2026
- 稿件说明：
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王广,宋昕桦,杨杰等.基于AMPK/SIRT1/NF-κB/NLRP3信号通路探讨柴胡加龙骨牡蛎汤对抑郁样大鼠的作用机制[J].中国实验方剂学杂志,2026,32(11):144-152.

WANG Guang,SONG Xinhua,YANG Jie,et al.Exploring Mechanism of Chaihu Jia Longgu Mulitang in Depressive-like Rats via AMPK/SIRT1/NF-κB/NLRP3 Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2026,32(11):144-152.
王广,宋昕桦,杨杰等.基于AMPK/SIRT1/NF-κB/NLRP3信号通路探讨柴胡加龙骨牡蛎汤对抑郁样大鼠的作用机制[J].中国实验方剂学杂志,2026,32(11):144-152. DOI： 10.13422/j.cnki.syfjx.20260167.

WANG Guang,SONG Xinhua,YANG Jie,et al.Exploring Mechanism of Chaihu Jia Longgu Mulitang in Depressive-like Rats via AMPK/SIRT1/NF-κB/NLRP3 Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2026,32(11):144-152. DOI： 10.13422/j.cnki.syfjx.20260167.

摘要

目的

探究柴胡加龙骨牡蛎汤对孤养联合慢性不可预见性温和应激（CUMS）模型大鼠类抑郁样行为及神经炎症的影响，并分析其可能机制。

方法

60只雄性SD大鼠随机分为正常组，模型组，柴胡加龙骨牡蛎汤低、中、高剂量组（2.89、5.78、11.56 g·kg

-1

）和氟西汀组（10 mg·kg

-1

）。除正常组外，其他各组采用孤养联合CUMS干预63 d，前35 d仅制备抑郁模型，第36天开始造模同时给药，共干预28 d。采用糖水偏好实验、旷场实验、强迫游泳实验评价大鼠类抑郁行为，苏木素-伊红（HE）染色观察海马组织形态学，免疫组化（IHC）检测海马离子钙结合衔接分子1（Iba1）和消皮素D（GSDMD）蛋白的表达水平；蛋白免疫印迹法（Western blot）检测海马区5′-腺苷酸活化蛋白激酶（AMPK）及磷酸化（p）-AMPK、沉默信息调节因子1（SIRT1）、核转录因子-

B（NF-

B）及p-NF-

B、NOD样受体蛋白3（NLRP3）和胱天蛋白酶-1（Caspase-1）的蛋白表达水平，实时荧光定量聚合酶链式反应（Real-time PCR）检测海马中肿瘤坏死因子-

（TNF-

）、白细胞介素（IL）-6和IL-1

mRNA表达水平。

结果

与正常组比较，模型组糖水偏好率降低（

0.01）；旷场实验总运动距离缩短（

0.01）、静止时间延长（

0.01），中央区停留时间减少（

0.01）；强迫游泳实验静止时间增加（

0.01）；海马神经元结构被破坏；海马组织中Iba1、GSDMD含量升高（

0.01）；海马组织中p-AMPK、SIRT1蛋白表达下调（

0.01）；p-NF-

B、NLRP3、Caspase-1蛋白表达上调（

0.01）；海马组织中IL-1

、IL-6、TNF-

mRNA上调（

0.01）。与模型组比较，柴胡加龙骨牡蛎汤低、中、高剂量组及氟西汀组均可逆转类抑郁样行为改变，表现为糖水偏好率提高、旷场总运动距离增加且静止时间缩短、中央区停留时间延长，以及强迫游泳静止时间减少（

0.05，

0.01）；同时减轻海马神经元结构损伤，在海马组织中下调Iba1、GSDMD表达，上调p-AMPK与SIRT1表达，并抑制p-NF-

B、NLRP3、Caspase-1及IL-1

、IL-6、TNF-

mRNA的异常升高（

0.05，

0.01）。

结论

柴胡加龙骨牡蛎汤可改善孤养联合CUMS模型大鼠类抑郁样行为并减轻海马神经炎症与细胞焦亡，提示其作用可能与调控AMPK/SIRT1/NF-

B/NLRP3信号通路有关。

Abstract

Objective

To investigate the effects of Chaihu Jia Longgu Mulitang（CJLM） on depression-like behaviors and neuroinflammation in rats subjected to social isolation combined with chronic unpredictable mild stress（CUMS）， and to explore the potential underlying mechanisms.

Methods

Sixty male SD rats were randomly divided into a normal group， a model group， and low-， medium-， and high-dose CJLM groups（2.89， 5.78， 11.56 g·kg

-1

）， as well as a fluoxetine group（10 mg·kg

-1

）. Except for the normal group， all other groups were subjected to social isolation combined with CUMS for 63 d. During the first 35 d， depression models were established only， and from day 36 onward， modeling and drug administration were conducted simultaneously for a total intervention period of 28 d. Depression-like behaviors were evaluated using the sucrose preference test， open-field test， and forced swimming test. Hematoxylin-eosin（HE） staining was performed to observe hippocampal histomorphology. Immunohistochemistry（IHC） was used to detect the expression levels of ionized calcium-binding adapter molecule 1（Iba1） and gasdermin D（GSDMD） proteins in the hippocampus. Western blot analysis was employed to determine the protein expression l

evels of adenosine 5′-monophosphate（AMP）-activated protein kinase（AMPK） and phosphorylated（p）-AMPK， silent information regulator 1（SIRT1）， nuclear factor-

B（NF-

B） and p-NF-

B， NOD-like receptor protein 3（NLRP3）， and Caspase-1 in the hippocampus. Real-time quantitative polymerase chain reaction（Real-time PCR） was used to detect the mRNA expression levels of tumor necrosis factor-

（TNF-

）， interleukin（IL）-6， and IL-1

in the hippocampus.

Results

Compared with the normal group， the model group showed a decreased sucrose preference rate（

0.01）， reduced total movement distance（

0.01）， prolonged immobility time（

0.01）， and decreased central zone residence time（

0.01） in the open-field test， and increased immobility time in the forced swimming test（

0.01）. Hippocampal neuronal structure was damaged. The contents of Iba1 and GSDMD in the hippocampus were significantly increased（

0.01）. The protein expression levels of p-AMPK and SIRT1 in the hippocampus were significantly decreased（

0.01）， whereas the protein expression levels of p-NF-

B， NLRP3， and Caspase-1 were significantly increased（

0.01）. The mRNA expression levels of IL-1

， IL-6， and TNF-

in the hippocampus were significantly upregulated（

0.01）. Compared with the model group， the low-， medium-， and high-dose CJLM groups and the fluoxetine group all were able to reverse depression-like behavioral changes， as evidenced by increased sucrose preference rate， increased total movement distance with shortened immobility time in the open-field test， prolonged central zone residence time， and reduced immobility time in the forced swimming test（

0.05，

0.01）. Mean

while， hippocampal neuronal structural damage was alleviated. In the hippocampus， the expression levels of Iba1 and GSDMD were downregulated， the expression levels of p-AMPK and SIRT1 were upregulated， and the abnormal elevations of p-NF-

B， NLRP3， Caspase-1， as well as IL-1

， IL-6， and TNF-

mRNA were suppressed（

0.05，

0.01）.

Conclusion

CJLM can ameliorate depression-like behaviors in rats subjected to social isolation combined with CUMS and attenuate hippocampal neuroinflammation and pyroptosis， suggesting that its effects may be associated with the regulation of AMPK/SIRT1/NF-

B/NLRP3 signaling pathway.

关键词

Keywords

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Exploring Mechanism of Chaihu Jia Longgu Mulitang in Depressive-like Rats via AMPK/SIRT1/NF-κB/NLRP3 Signaling Pathway

DOI：10.13422/j.cnki.syfjx.20260167

摘要

Abstract

关键词

Keywords

references