电针对慢性阻塞性肺疾病大鼠模型胆碱能抗炎通路的调节作用。
Electro-acupuncture regulates the cholinergic anti-inflammatory pathway in a rat model of chronic obstructive pulmonary disease.
机构信息
Department of Physiology, College of Integrated Traditional Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, Anhui Province, China.
Institute of Acu-Moxibustion and Meridian, College of Acupuncture and Tuina, Anhui University of Chinese Medicine, Hefei 230012, Anhui Province, China.
出版信息
J Integr Med. 2018 Nov;16(6):418-426. doi: 10.1016/j.joim.2018.10.003. Epub 2018 Oct 6.
OBJECTIVE
Acupuncture has a definite therapeutic effect on chronic obstructive pulmonary disease (COPD), and the cholinergic anti-inflammatory pathway (CAP) has been shown to be involved in regulation of inflammation. In this study, we investigated whether electro-acupuncture (EA) affects the CAP in COPD.
METHODS
Sprague-Dawley rats were induced into COPD through exposure to cigarette smoke combined with lipopolysaccharide. EA treatment was applied at Zusanli (ST36) and Feishu (BL13) points for 30 min/d for 7 d. Seventy-two rats were randomly divided into six study groups, including normal, normal + EA, normal + α-bungarotoxin (α-BGT) (the antagonist of the nicotinic acetylcholine receptor α7 subunit (α7nAChR)) + EA, COPD, COPD + EA, and COPD + α-BGT + EA. Lung function, pathology and vagus nerve discharge were tested. The levels of acetylcholine (ACh), acetylcholinesterase (AChE), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF) and lung tissue were measured by enzyme-linked immunosorbent assay. The mRNA and protein expression and immunoreactivity of α7nAChR and its postreceptor inflammation signal pathway, including janus kinase 2 (JAK2), signal transducers and activators of transcription 3 (STAT3), nuclear factor-κB (NF-κB), were observed by quantitative reverse transcription-polymerase chain reaction, Western blot and immunohistochemistry.
RESULTS
Compared with normal rats, there were a significant decline in lung function and discharge of the vagus nerve (P < 0.01), a marked sign of lung inflammation and an increase of ACh, AChE, IL-6 and TNF-α level in BALF or lung tissue (P < 0.05, P < 0.01) and higher expression of α7nAChR, JAK2, STAT3 and NF-κB (P < 0.05, P < 0.01) in the COPD rats. In rats receiving EA, the lung function and vagal discharge were enhanced (P < 0.01), lung inflammation was improved and the levels of ACh, AChE, IL-6 and TNF-α were decreased (P < 0.01). Further, the expression of α7nAChR, JAK2, STAT3 and NF-κB was downregulated (P < 0.05, P < 0.01). However, the above effects of EA were blocked in rats injected with α-BGT (P < 0.01).
CONCLUSION
EA treatment can reduce the lung inflammatory response and improve lung function in COPD, which may be related to its involvement in the regulation of CAP.
目的
针刺对慢性阻塞性肺疾病（COPD）有明确的治疗作用，胆碱能抗炎途径（CAP）已被证明参与了炎症的调节。本研究旨在探讨电针对 COPD 中 CAP 的影响。
方法
将 Sprague-Dawley 大鼠暴露于香烟烟雾和脂多糖中，诱导 COPD。EA 治疗应用于足三里（ST36）和肺俞（BL13）点，每天 30 分钟，共 7 天。72 只大鼠随机分为六组，包括正常组、正常+EA 组、正常+α-银环蛇毒素（α-BGT）（烟碱型乙酰胆碱受体α7 亚基（α7nAChR）的拮抗剂）+EA 组、COPD 组、COPD+EA 组和 COPD+α-BGT+EA 组。检测肺功能、病理和迷走神经放电。酶联免疫吸附试验测定支气管肺泡灌洗液（BALF）和肺组织中乙酰胆碱（ACh）、乙酰胆碱酯酶（AChE）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的水平。通过定量逆转录-聚合酶链反应、Western blot 和免疫组织化学观察α7nAChR 及其受体后炎症信号通路，包括 Janus 激酶 2（JAK2）、信号转导和转录激活因子 3（STAT3）、核因子-κB（NF-κB）的 mRNA 和蛋白表达及免疫反应性。
结果
与正常大鼠相比，COPD 大鼠肺功能和迷走神经放电明显下降（P<0.01），肺炎症明显，BALF 或肺组织中 ACh、AChE、IL-6 和 TNF-α水平升高（P<0.05，P<0.01），α7nAChR、JAK2、STAT3 和 NF-κB 的表达增加（P<0.05，P<0.01）。在接受 EA 治疗的大鼠中，肺功能和迷走神经放电增强（P<0.01），肺炎症改善，ACh、AChE、IL-6 和 TNF-α水平降低（P<0.01）。此外，α7nAChR、JAK2、STAT3 和 NF-κB 的表达下调（P<0.05，P<0.01）。然而，在注射α-BGT 的大鼠中，EA 的上述作用被阻断（P<0.01）。
结论
EA 治疗可减轻 COPD 大鼠的肺炎症反应，改善肺功能，这可能与其参与 CAP 的调节有关。
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