Effects of acupuncture on NLRP3 inflammasome and inflammatory cytokines in the hippocampus of chronic stress rat model of depression

WEI Gaowen; WU Jihong; WANG Hongmei; SHAO Ruijie; LU Jun; TU Ya

doi:10.3969/j.issn.1006-2157.2023.03.021

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Effects of acupuncture on NLRP3 inflammasome and inflammatory cytokines in the hippocampus of chronic stress rat model of depression

Acupuncture Moxibustion and Tuina | 更新时间：2023-04-07

- Effects of acupuncture on NLRP3 inflammasome and inflammatory cytokines in the hippocampus of chronic stress rat model of depression
- Journal of Beijing University of Traditional Chinese Medicine Vol. 46, Issue 3, Pages: 427-434(2023)
- 作者机构：
  
  1.北京中医药大学针灸推拿学院　北京　100029
  2.浙江省丽水市第二人民医院
- 作者简介：
  
  Prof. LU Jun, Ph.D., Master’s Supervisor. Beijing University of Chinese Medicine, No. 11, Beisanhuan Donglu Road, Chaoyang District, Beijing 100029. E-mail: lumed@126.com
- 基金信息：
  
  National Natural Science Foundation of China(81774418;82174508)
- DOI：10.3969/j.issn.1006-2157.2023.03.021
  CLC： R246.6
- Received：18 September 2022，
  
  Published：30 March 2023
- 稿件说明：
移动端阅览
WEI Gaowen, WU Jihong, WANG Hongmei, et al. Effects of acupuncture on NLRP3 inflammasome and inflammatory cytokines in the hippocampus of chronic stress rat model of depression[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023, 46(3): 427-434.
DOI：

WEI Gaowen, WU Jihong, WANG Hongmei, et al. Effects of acupuncture on NLRP3 inflammasome and inflammatory cytokines in the hippocampus of chronic stress rat model of depression[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023, 46(3): 427-434. DOI： 10.3969/j.issn.1006-2157.2023.03.021.

摘要

目的

探讨针刺治疗抑郁症的作用机制。

方法

将SD大鼠随意分为正常组、模型组、针刺组、氟西汀组，每组8只。大鼠抑郁症模型采用慢性不可预知温和应激的方法制备。针刺组每天造模前针刺“百会”和“印堂”穴，每次10 min，每周6次；氟西汀组每天造模前灌胃氟西汀(10 mg/kg)，每日1次。检测大鼠体质量和糖水偏好百分率；采用蛋白质印迹法检测海马核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)、凋亡相关斑点样蛋白(ASC)、半胱氨酸天冬氨酸蛋白酶－1(Caspase-1)的蛋白表达；采用实时荧光定量PCR检测海马促炎细胞因子白细胞介素(IL)－1β与IL-18的基因表达；采用酶联免疫吸附法检测海马IL-1β、IL-18，以及抗炎细胞因子IL-4、IL-10的含量。

结果

与正常组相比，模型组体质量下降(

0.05)，糖水偏好百分率降低(

0.01)，海马NLRP3、ASC和Caspase-1的蛋白表达升高(

0.01)，海马IL-1β、IL-18的基因表达与含量均升高(

0.01、

0.05)，海马IL-4、IL-10含量降低(

0.01、

0.05)。与模型组相比，针刺组、氟西汀组体质量差异无统计学意义(

0.05)，糖水偏好百分率提高(

0.05)，海马NLRP3、ASC和Caspase-1蛋白表达降低(

0.01)，海马IL-1β基因和IL-18基因表达降低(

0.01、

0.05)，IL-1β和IL-18含量降低(

0.01、

0.05)，海马IL-10含量升高(

0.05)，而IL-4的含量变化差异无统计学意义(

0.05)。针刺组与氟西汀组比较，两组间差异无统计学意义(

0.05)。

结论

针刺能够改善慢性应激大鼠抑郁样行为、发挥抗抑郁作用，其机制可能与抑制海马NLRP3炎性小体激活及其介导的炎症反应，减少促炎细胞因子，提高抗炎细胞因子水平有关。

Abstract

Objective

To inquire into the mechanism of acupuncture in the treatment of depression.

Methods

Sprague-Dawley rats were randomly divided into the normal group

the model group

the acupuncture group

and the fluoxetine group (

=8 rats in each). The depression model was established by using chronic unpredictable mild stress method. The "Baihui" (GV20) and "Yintang" (GV29) acupoints were selected in the acupuncture group. Acupuncture treatment was given before modeling each day

with needle retention for 10 minutes

six times a week. Fluoxetine was given intragastrically before modeling each day (10 mg/kg)

once daily. The behavior tests

including the body weight and the sucrose preference test were performed. The hippocampal protein expression levels of NLRP3

ASC

and Caspase-1 were measured by Western blotting. The hippocampal gene expression levels of IL-1β and IL-18 were measured by real-time fluorescent quantitative PCR. The hippocampal contents of IL-1β

IL-18

IL-4

and IL-10 were measured by ELISA.

Results

Compared with the normal group

the body weight and the percentage of sucrose preference test were decreased in the model group (

0.05

0.01)

the hippocampal expression levels of NLRP3

ASC

and Caspase-1 were increased (

0.01)

the hippocampal gene expression of the pro-inflammatory factors IL-1β and IL-18 were increased (

0.01

0.05)

and the protein levels of IL-1β and IL-18 in the hippocampus were increased (

0.01

0.05)

and the levels of anti-inflammatory factors IL-4 and IL-10 were decreased (

0.01

0.05). Compared with the model group

there was no statistical difference in the body weight in the acupuncture and fluoxetine groups (

0.05)

while the percentage of sucrose preference was increased in both the acupuncture and fluoxetine groups (

0.05). Compared with the model group

the expression levels of hippocampal NLRP3

ASC

and Caspase-1 were decreased (

0.01)

the gene expression levels of the pro-inflammatory factors IL-1β and IL-18 (

0.01

0.05) and the protein levels of IL-1β and IL-18 were reduced (

0.01

0.05)

and the content of the anti-inflammatory factor IL-10 in the hippocampus was increased (

0.05). However

there was no statistical difference in the content of IL-4 (

0.05). In addition

there was no statistical difference between the acupuncture and fluoxetine groups (

0.05).

Conclusion

Acupuncture treatment could alleviate depressive behavior and exert antidepressant effects

possibly by inhibiting the NLRP3 inflammasome activity and the related inflammatory response

reducing pro-inflammatory cytokine levels

and increasing anti-inflammatory cytokine levels in the hippocampus.

关键词

Keywords

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