Electroacupuncture at Feishu(BL13) and Zusanli(ST36) down-regulates the expression of orexins and their receptors in rats with chronic obstructive pulmonary disease

OBJECTIVE: Infl ammation 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 infl ammation 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 fl uid(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 signifi cantly decreased in the rats with COPD(P<0.05). There were obvious 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 1 type receptor(OXR1) and OX 2 type receptor(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 orexin B, levels in lung tissue also decreased(P<0.01), as did mRNA expression of OX1 R and OX2 R 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).CONCLUSION: EA at Zusanli and Feishu improved lung function of rats with COPD and had an anti-infl ammatory effect, which may be related to down-regulation of OXA and its receptors.