title: Electroacupuncture at Feishu (BL13) and Zusanli (ST36) down-regulates the expression of orexins and their receptors in rats with chronic obstructive pulmonary disease.
abstract: OBJECTIVE
  Inflammation and lung function decline are the main pathophysiological features of chronic obstructive pulmonary disease (COPD). Acupuncture can improve lung function in patients with COPD, but the underlying mechanisms are not well understood. Orexins (OXs), which are found in peripheral plasma, are neuropeptides that regulate respiration and their levels are related to COPD. Therefore, we hypothesized that acupuncture might alter OXs, reduce lung inflammation and improve lung function in COPD.
  
  
  METHODS
  COPD was induced in rats by exposure to cigarette smoke for 8 weeks and injecting with lipopolysaccharide twice. Electroacupuncture (EA) was performed at Feishu (BL13) and Zusanli (ST36) for 30 min/d for 2 weeks. Rat lung function and morphology were assessed after EA. The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF) and orexin A and B levels in the lung tissue were detected by enzyme-linked immunosorbent assay. OX receptor mRNA levels and immunopositive cells were assessed with real-time polymerase chain reaction and immunohistochemical methods, respectively. The relationships among lung function, cell factors, and OX levels were analyzed by Pearson correlation analyses.
  
  
  RESULTS
  Compared with the control group, lung function was significantly decreased in the rats with COPD (P<0.05). There were increases in TNF-α and IL-1β levels in BALF (P<0.05 and P<0.01, respectively), orexin A level in lung tissue (P<0.01; but not orexin B) and mRNA expressions of OX (OXR1) and OX 2 (OXR2) in lung tissue (P<0.05 and P<0.01, respectively); the integrative optical densities (IODs) of both receptors were greater in the COPD group (P<0.05). For rats with COPD subjected to EA, lung function was improved (P<0.05). There were notable decreases in TNF-α and IL-1β levels (P<0.05 and <0.01, respectively) in BALF. Orexin A, but not orexinB, levels in lung tissue also decreased (P<0.01), as did mRNA expression of OX1R and OX2R in lung tissue (P<0.05 and P<0.01, respectively). Receptor IODs were also reduced after EA treatment (P<0.05). Furthermore, orexin A levels and ratio of forced expiratory volume in 0.3 s to forced vital capacity were strongly negatively correlated (P<0.01), and orexin A was positively correlated with TNF-α and IL-1β (P<0.001 and P<0.05, respectively).
  
  
  CONCLUSIONS
  EA at Zusanli and Feishu improved lung function of rats with COPD and had an anti-inflammatory effect, which may be related to down-regulation of OXA and its receptors.
authors.affiliation: Department of Physiology, College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230038, Anhui Province, China.
authors.forename: Xin-fang
authors.initials: XF
authors.lastname: Zhang
authors.affiliation: The Third Clinical College of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang Province, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, Shanghai Medical College of Fudan University, Shanghai 200032, China.
authors.forename: Wen-ye
authors.initials: WY
authors.lastname: Geng
authors.affiliation: Department of Physiology, College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230038, Anhui Province, China.
authors.forename: Shu-jun
authors.initials: SJ
authors.lastname: Zhao
authors.affiliation: Department of Physiology, College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230038, Anhui Province, China.
authors.forename: Chuan-wei
authors.initials: CW
authors.lastname: Jiang
authors.affiliation: Department of Physiology, College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230038, Anhui Province, China.
authors.forename: Sheng-rong
authors.initials: SR
authors.lastname: Cai
authors.affiliation: Institute of Acupuncture and Meridian, College of Acupuncture and Osteology, Anhui University of Chinese Medicine, Hefei 230038, Anhui Province, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Institute of Acupuncture and Meridian, College of Acupuncture and Osteology, Anhui University of Chinese Medicine, Hefei 230038, Anhui Province, China.
authors.forename: Chuan-yun
authors.initials: CY
authors.lastname: Zhou
authors.affiliation: Department of Physiology, College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230038, Anhui Province, China; E-mail: zibingliu@163.com.
authors.forename: Zi-bing
authors.initials: ZB
authors.lastname: Liu
mesh_terms: D000818:Animals; D015536:Down-Regulation; D015671:Electroacupuncture; D053583:Interleukin-1beta / Q000032:analysis; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis* / Q000235:genetics; D008168:Lung / Q000503:physiopathology; D008297:Male; D009479:Neuropeptides / Q000032:analysis* / Q000235:genetics; D064446:Orexin Receptors / Q000032:analysis* / Q000235:genetics; D000068797:Orexins; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D053583:Interleukin-1beta; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D014409:Tumor Necrosis Factor-alpha