Alpha7 nicotinic acetylcholine receptor activation attenuated intestine-derived acute lung injury

• Published in: The Journal of surgical research 2016-04, Vol.201 (2), p.258-265
• Main Authors: He, Ye, MD, Ye, Zhi-Qiang, PhD, Li, Xiang, PhD, Zhu, Guo-Song, MD, Liu, Yue, MD, Yao, Wei-Feng, MD, Luo, Gang-Jian, PhD
• Format: Article
• Language: English
• Subjects: Acute lung injury; Acute Lung Injury - etiology; Acute Lung Injury - metabolism; Acute Lung Injury - prevention & control; alpha7 Nicotinic Acetylcholine Receptor - agonists; Animals; Apoptosis; Apoptosis - drug effects; Benzamides - pharmacology; Benzamides - therapeutic use; Bridged Bicyclo Compounds - pharmacology; Bridged Bicyclo Compounds - therapeutic use; Drug Evaluation, Preclinical; Intestinal ischemia–reperfusion; Intestines - blood supply; Lung - drug effects; Lung - metabolism; NF-kappa B - metabolism; Random Allocation; Rats, Sprague-Dawley; Reperfusion Injury - complications; Signal Transduction - drug effects; Surgery; TLR4/NF-κB; Toll-Like Receptor 4 - metabolism; α7nAChR
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2015.10.046

Abstract Background Intestinal ischemia–reperfusion (IIR) could lead to acute lung injury, associated with severe alveolar epithelial cells inflammatory and oxidative injury. Alpha7 nicotinic acetylcholine receptor (α7nAChR) is an essential component of the cholinergic anti-inflammatory pathway. The aim of this study was to investigate the important role of α7nAChR on the lung subjected to IIR. Methods Thirty-two Sprague–Dawley rats were randomly divided into four groups ( n  = 8 in each): sham group (group S), model group (group M), α7nAChR agonist PNU-282987-treated group (group PNU), and specific α7nAChR antagonist methyllycaconitine-treated group (group MLA). Intestinal IR damage was induced by clamping the superior mesenteric artery for 75 min, followed by a 120-min reperfusion. All rats were killed at 2 h after release of the clamps. The histologic examination of lungs was made, and lung water content was detected. Expression levels of malondialdehyde, tumor necrosis factor alpha, interleukin-6, and superoxide dismutase activity of the lungs were detected. Additionally, expression level of toll-like receptor (TLR)4 and nuclear factor-kappaB (NF-κB p65) in the nucleus of lung tissue and apoptosis-related protein (Bax, Bcl-2, and cleaved-caspase3) were detected using Western blot. Results Lungs were damaged after intestine IR, manifested by higher lung water content, histologic score, concentrations of interleukin-6, tumor necrosis factor alpha, and malondialdehyde of group M than those of group S, accompanied with decreased superoxide dismutase activity ( P