Electroacupuncture Attenuates Immune-Inflammatory Response in Hippocampus of Rats with Vascular Dementia by Inhibiting TLR4/MyD88 Signaling Pathway

Yu BU; Wen-shuang LI; Ji LIN; Yu-wei WEI; Qiu-ying SUN; Shi-jie ZHU; Zhong-sheng TANG

doi:10.1007/s11655-021-3350-5

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Electroacupuncture Attenuates Immune-Inflammatory Response in Hippocampus of Rats with Vascular Dementia by Inhibiting TLR4/MyD88 Signaling Pathway

Acupuncture Research | Updated：2022-02-22

- Electroacupuncture Attenuates Immune-Inflammatory Response in Hippocampus of Rats with Vascular Dementia by Inhibiting TLR4/MyD88 Signaling Pathway
- Chinese Journal of Integrative Medicine Vol. 28, Issue 2, Pages: 153-161(2022)
- Affiliations：
  
  1.School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang (550025), China
  2.Department of Hematology, the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang (550025), China
- Author bio：
  
  Prof. TANG Zhong-sheng, E-mail:tangzhongsheng297@gzy.edu.cn
- Funds：
- DOI：10.1007/s11655-021-3350-5
  CLC：
- Published：01 February 2022，
  
  Published Online：15 December 2021，
  
  Accepted：22 October 2021
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Yu BU, Wen-shuang LI, Ji LIN, et al. Electroacupuncture Attenuates Immune-Inflammatory Response in Hippocampus of Rats with Vascular Dementia by Inhibiting TLR4/MyD88 Signaling Pathway. [J]. Chinese Journal of Integrative Medicine 28(2):153-161(2022)
DOI：

Yu BU, Wen-shuang LI, Ji LIN, et al. Electroacupuncture Attenuates Immune-Inflammatory Response in Hippocampus of Rats with Vascular Dementia by Inhibiting TLR4/MyD88 Signaling Pathway. [J]. Chinese Journal of Integrative Medicine 28(2):153-161(2022) DOI： 10.1007/s11655-021-3350-5.

摘要

目的:

观察电针 (EA) 是否通过Toll样受体4 (TLR4) /髓样分化因子88 (MyD88) 信号通路降低血管性痴呆 (VaD) 大鼠的免疫炎症反应

起到改善VaD大鼠的认知障碍.

方法:

本实验按随机数字表法将SD大鼠分为8组

包括假手术组 (sham) 、模型组 (4-VO) 、电针组 (4-VO+EA) 、非穴位电针组 (4-VO+non-EA) 、正常大鼠电针组 (sham+EA) 、激动剂组 (4-VO+LPS)、激动剂+电针组 (4-VO+LPS+EA) 和抑制剂组 (4-VO+TAK-242) . 采用改良四血管阻断法 (4-VO) 建立VaD大鼠模型

给予4-VO+LPS和4-VO+LPS+EA组大鼠侧脑室注射TLR4激动剂LPS

4-VO+TAK-242组大鼠侧脑室注射TLR4抑制剂TAK-242. 并于7天后

取百会 (DV 20) 、膻中 (RN 17) 、膈俞 (BL 17) 、气海 (RN 6) 和三阴交 (SP 6) 5个穴位给予4-VO+EA、sham+EA、4-VO+LPS+EA组大鼠电针刺激

4-VO+non-EA组大鼠非穴位电针刺激

每天一次

连续3周. 治疗结束前后采用水迷宫观察大鼠学习记忆功能

治疗结束后检测大鼠淋巴细胞亚群、淋巴细胞转化率、白细胞介素6(IL-6)和肿瘤坏死因子α (TNF-α)表达含量

评估VaD大鼠的免疫功能和炎症水平

透射电镜观察海马神经细胞的超微结构

采用Western Blot检测大鼠海马内TLR4、MyD88蛋白表达含量

Real-time PCR检测大鼠海马内TLR4、MyD88、IL-6、TNF-αmRNA表达水平

Elisa检测大鼠血清中IL-6、TNF-α表达水平.

结果:

与4-VO组相比

4-VO+EA组电针显着改善大鼠免疫功能

抑制大鼠海马TLR4、MyD88蛋白和mRNA表达

降低血清IL-6表达和TNF-α (均

0.05或

0.01)

并导致海马神经元修复. 4-VO+LPS+EA和4-VO+EA组之间、4-VO+TAK-242和4-VO+EA组之间均无显着差异 (

0.05) .

结论:

电针通过抑制 TLR4/MyD88 信号通路减轻与免疫炎症相关的认知障碍

EA可能是治疗VaD的一种有前景的替代疗法.

Abstract

Objective:

To investigate whether electroacupuncture (EA) alleviates cognitive impairment by suppressing the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway

which triggers immune-inflammatory responses in the hippocampus of rats with vascular dementia (VaD).

Methods:

The experiments were conducted in 3 parts and in total the Sprague-Dawley rats were randomly divided into 8 groups by a random number table

including sham

four-vessel occlusion (4-VO)

4-VO+EA

4-VO+non-EA

sham+EA

4-VO+lipopolysaccharide (LPS)

4-VO+LPS+EA

and 4-VO+TAK-242 groups. The VaD model was established by the 4-VO method. Seven days later

rats were treated with EA at 5 acupoints of Baihui (DV 20)

Danzhong (RN 17)

Geshu (BL 17)

Qihai (RN 6) and Sanyinjiao (SP 6)

once per day for 3 consecutive weeks. Lymphocyte subsets

lymphocyte transformation rates

and inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were measured to assess immune function and inflammation in VaD rats. Transmission electron microscopy was used to observe the ultrastructure of nerve cells in the hippocampus. The levels of TLR4

MyD88

IL-6

and TNF-α were detected after EA treatment. TLR4/MyD88 signaling and cognitive function were also assessed after intracerebroventricular injection of TLR4 antagonist TAK-242 or TLR4 agonist LPS with or without EA.

Results:

Compared with the 4-VO group

EA notably improved immune function of rats in the 4-VO+EA group

inhibited the protein and mRNA expressions of TLR4 and MyD88 in the hippocampus of rats

reduced the expressions of serum IL-6 and TNF-α (all

0.05 or

0.01)

and led to neuronal repair in the hippocampus. There were no significant differences between the 4-VO+LPS+EA and 4-VO+EA groups

nor between the 4-VO+TAK-242 and 4-VO+EA groups (

0.05).

Conclusions:

EA attenuated cognitive impairment associated with immune inflammation by inhibition of the TLR4/MyD88 signaling pathway. Thus

EA may be a promising alternative therapy for the treatment of VaD.

关键词

Keywords

electroacupuncturevascular dementiaimmune-inflammationtoll-like receptor 4/myeloid differentiation factor 88 signaling pathway

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