基于胆碱能抗炎通路探讨电针对自发性高血压大鼠心肌纤维化的影响

辛娟娟; 周晨; 吴爽; 张雯晰; 刘群; 赵玉雪; 喻晓春; 高俊虹

doi:10.13703/j.0255-2930.20221111-k0004

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基于胆碱能抗炎通路探讨电针对自发性高血压大鼠心肌纤维化的影响

机制探讨1 | 更新时间：2024-06-03

- 基于胆碱能抗炎通路探讨电针对自发性高血压大鼠心肌纤维化的影响
- Effect of electroacupuncture on myocardial fibrosis in spontaneously hypertensive rats based on cholinergic anti-inflammatory pathway
- 中国针灸 2023年43卷第10期页码：1151-1156
- 作者机构：
  
  中国中医科学院针灸研究所，北京 100700
- 作者简介：
  
  高俊虹，研究员。E-mail：gaojh@mail.cintcm.ac.cn
- 基金信息：
  
  国家自然科学基金资助项目(81804211);中国中医科学院基本科研业务费优秀青年科技人才项目（创新类）：ZZ13-YQ-065
- DOI：10.13703/j.0255-2930.20221111-k0004
  中图分类号： R 245.9⁺7
- 收稿：2022-11-11，
  
  纸质出版：2023-10-12
- 稿件说明：
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辛娟娟,周晨,吴爽等.基于胆碱能抗炎通路探讨电针对自发性高血压大鼠心肌纤维化的影响[J].中国针灸,2023,43(10):1151-1156.

XIN Juan-juan,ZHOU Chen,WU Shuang,et al.Effect of electroacupuncture on myocardial fibrosis in spontaneously hypertensive rats based on cholinergic anti-inflammatory pathway[J].Chinese Acupuncture & Moxibustion,2023,43(10):1151-1156.
辛娟娟,周晨,吴爽等.基于胆碱能抗炎通路探讨电针对自发性高血压大鼠心肌纤维化的影响[J].中国针灸,2023,43(10):1151-1156. DOI： 10.13703/j.0255-2930.20221111-k0004.

XIN Juan-juan,ZHOU Chen,WU Shuang,et al.Effect of electroacupuncture on myocardial fibrosis in spontaneously hypertensive rats based on cholinergic anti-inflammatory pathway[J].Chinese Acupuncture & Moxibustion,2023,43(10):1151-1156. DOI： 10.13703/j.0255-2930.20221111-k0004.

摘要

目的

观察电针“内关”对自发性高血压大鼠（SHR）心肌纤维化（MF）的影响，并初步探究胆碱能抗炎通路（CAP）及其下游核因子κB（NF-κB）信号通路的介导作用。

方法

选用12周龄雄性WKY大鼠6只为正常组，另选12周龄SHR 18只，随机分为模型组、电针组和α7烟碱型乙酰胆碱受体（α7nAchR）阻断后电针组（α7阻断后电针组），每组6只。电针组取“内关”及其左侧旁开0.5 cm处电针干预，选择疏密波，频率2 Hz/15 Hz，电流强度1 mA，每次30 min，隔日1次，干预8周；α7阻断后电针组于每次电针前尾静脉注射α7nAchR特异性阻断剂α-银环蛇毒素。电针干预结束后，采用无创血压仪检测各组大鼠收缩压（SBP）、舒张压（DBP）、平均动脉压（MAP），超声心动图检测左室舒张末期前壁厚度（LVAWd）、左室舒张末期后壁厚度（LVPWd）及舒张末期左室内径（LVIDd），碱水解法检测大鼠心肌组织羟脯氨酸（Hyp）含量，ELISA法检测大鼠心肌组织乙酰胆碱（Ach）含量，实时荧光定量PCR法检测心肌组织NF-κB p65、肿瘤坏死因子α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）mRNA表达。

结果

与正常组比较，模型组大鼠SBP、DBP、MAP、LVAWd、LVPWd均升高（

0.01），LVIDd降低（

0.01）。与模型组比较，电针组SBP、DBP、MAP、LVAWd 均降低（

0.01，

0.05），LVIDd升高（

0.01）。α7阻断后电针组上述指标与模型组比较差异无统计学意义（

0.05）。与正常组比较，模型组心肌组织Hyp含量及NF-κB p65、TNF-α、IL-1β、IL-6 mRNA表达均升高（

0.01，

0.05），Ach含量降低（

0.01）。与模型组比较，电针组心肌组织Hyp含量及NF-κB p65、TNF-α、IL-1β、IL-6 mRNA表达均降低（

0.05，

0.01），Ach含量升高（

0.01）；α7阻断后电针组上述指标与模型组比较差异无统计学意义（

0.05）。

结论

CAP可能在电针“内关”改善SHR心肌纤维化病理损害中发挥了作用，其机制可能与增加迷走神经递质Ach含量、降低心肌组织NF-κB p65及促炎因子（TNF-α、IL-1β、IL-6） mRNA表达有关。

Abstract

Objective

To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHR)

and explore preliminarily the mediating role of cholinergic anti-inflammatory pathway (CAP) and its downstream nuclear factor κB (NF-κB) signaling pathway.

Methods

Six 12-week-old WKY male rats were employed as the normal group. Eighteen 12-week-old SHR were randomly divided into 3 groups

i.e. a model group

an EA group and a blocking group (EA after blocking α7 nicotinic acetylcholine receptor [α7nAchR])

with 6 rats in each one. In the EA group

EA was delivered at "Neiguan"(PC 6) and the site 0.5 cm from its left side

with disperse-dense wave

2 Hz/15 Hz in frequency and 1 mA in current intensity. One intervention took 30 min and was given once every 2 days

lasting 8 weeks. In the blocking group

prior to each EA

the α7nAchR specific blocker

α-bungartoxin was injected intravenously in the tails of the rats. After EA intervention

the systolic blood pressure (SBP)

the diastolic blood pressure (DBP) and the mean arterial pressure (MAP) were measured with non-invasive blood pressure monitor. Using echocardiogram

the left ventricular (LV) anterior wall end-diastolic thickness (LVAWd)

LV posterior wall end-diastolic thickness (LVPWd) and the LV end-diastolic internal diameter (LVIDd) were measured. The level of hydroxyproline (Hyp) in the myocardial tissue was determined by using alkaline hydrolysis

and that of acetylcholine (Ach) was detected by ELISA. With the real-time PCR adopted

the mRNA expression of NF-κB p65

tumor necrosis factor α (TNF-α)

interleukin (IL)-1β and IL-6 were determined.

Results

Compared with the normal group

SBP

DBP

MAP

LVAWd and LVPWd were increased (

0.01)

and LVIDd was decreased (

0.01) in the rats of the model group. SBP

DBP

MAP and LVAWd were dropped (

0.01

0.05)

and LVIDd rose (

0.01) in the EA group when compared with those in the model group. The differences in the above indexes were not statistically significant between the blocking group and the model gr

oup (

0.05). Compared with the normal group

Hyp level and the mRNA expression of NF-κB p65

TNF-α

IL-1β and IL-6 in the myocardial tissue increased (

0.01

0.05) and Ach level decreased (

0.01) in the model group. Hyp level

the mRNA expression of NF-κB p65

TNF-α

IL-1β and IL-6 in the myocardial tissue were reduced (

0.05

0.01) and Ach level rose (

0.01) in the EA group when compared with those in the model group. These indexes were not different statistically between the blocking group and the model group (

0.05).

Conclusion

CAP may be involved in ameliorating the pathological damage of myocardial fibrosis during EA at "Neiguan"(PC 6). The underlying effect mechanism is associated with up-regulating the neurotransmitter

Ach and down-regulating mRNA expression of NF-κB p65 and pro-inflammatory factors such as TNF-α

IL-1β and IL-6 in myocardial tissue.

关键词

Keywords

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