Role of α7nAChR in reduction of endotoxin-induced acute lung injury by limb ischemic preconditioning in mice / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of α7 nicotinic acetylcholine receptor (α7nAChR) in reduction of endotoxin-induced acute lung injury (ALI) by limb ischemic preconditioning in mice.Methods Eighty healthy male C57BL/6 mice,aged 8-10 weeks,weighing 22-26 g,were randomly divided into 5 groups (n =16 each) using a random number tablecontrol group (group C),ALI group,limb ischemic preconditioning group (group P),α-bungarotoxin (α-BGT) group,and limb ischemic preconditioning +α-BGT group (group P+α-BGT).Normal saline 100 μl was intratracheally instilled in group C.In group ALI,lipopolysaccharide 5 mg/kg was intratracheally instilled (in normal saline) to establish the model of endotoxin-induced ALI.In group P,the mice were subjected to 6 cycles of 5-min ischemia of the right hindlimb followed by 5-min reperfusion,and then the model of ALI was established.In group α-BGT,α-BGT 1 μg/kg was injected intraperitoneally before establishment of the model.In group P+α-BGT,limb ischemic preconditioning was performed,α-BGT 1 μg/kg was then injected intraperitoneally,and the model of ALI was established.At 24 h after LPS instillation,6 mice were selected from each group and sacrificed,and lungs were removed for microscopic examination and for determination of wet and dry lung weight,myeloperoxidase (MPO) activities,contents of interleukin-lbeta (IL-1β),tumor necrosis factoralpha (TNF-α) and IL-6,and expression of α7nAChR and high mobility group box-1 (HMGB1) in lung tissues.The lung water content was calculated.The survival of the left 10 mice in each group was observed at 7 days after establishment of the model,and the survival rate was calculated.Results Compared with group C,the lung water content,MPO activities,contents of IL-1β,TNF-α and IL-6,and HMGB1 expression were significantly increased,α7nAChR expression was significantly down-regulated,and the 7-day survival rate was significantly decreased in group ALI(P＜0.05).Compared with group ALI,the lung water content,MPO activities,contents of IL-1β,TNF-α and IL-6,and HMGB1 expression were significantly decreased,α7nAChR expression was significantly up-regulated,and the 7-day survival rate was significantly increased in group P (P＜0.05).Compared with group P,the lung water content,MPO activities,contents of IL-1β,TNF-α and IL-6,and HMGB1 expression were significantly increased,α7nAChR expression was significantly down-regulated,and the 7-day survival rate was significantly decreased in group P+α-BGT (P＜0.05).Conclusion The mechanism by which limb ischemic preconditioning inhibits inflammatory responses and reduces endotoxin-induced ALI is related to activation of α7nAChR in mice.