摘要
目的评价α7型烟碱乙酰胆碱受体（α7nAChR）在肢体缺血预处理减轻小鼠内毒素性急性肺损伤中的作用。方法清洁级健康雄性C57BL／6小鼠80只，8～10周龄，体重22～26g。采用随机数字表法分为5组（n=16）：对照组（C组）、急性肺损伤组（ALI组）、肢体缺血预处理组（P组）、α-银环蛇毒素组（α—BGT组）和肢体缺血预处理＋α-银环蛇毒素组（P＋α-BGT组）。C组气管内滴人100μl生理盐水；ALI组通过气管内滴入5mg／kg脂多糖（溶于生理盐水）制备小鼠内毒素性急性肺损伤模型；P组行肢体缺血预处理（6个循环的右后肢缺血5min、再灌注5min），随后制备小鼠内毒素性急性肺损伤模型；α-BGT组于模型制备前腹腔注射α-银环蛇毒素1μg／kg；P＋α—BGT组行肢体缺血预处理，随后腹腔注射α-银环蛇毒素1μg／kg并制备小鼠内毒素性急性肺损伤模型。于气管内滴入脂多糖后24h时每组随机取6只小鼠处死取肺组织，光镜下观察病理学结果，测定肺湿干重，计算肺水含量、髓过氧化物酶（MPO）活性、IL-1β、TNF—α、IL-6含量、α7nAChR及高迁移率族蛋白1（HMGB1）的表达水平，每组余10只小鼠观察7d内生存情况。结果与C组比较，ALI组肺水含量、MPO活性、IL-1β、TNF—α、IL-6含量和HMGB1表达水平升高，α7nAChR表达下调，7d生存率降低（P〈0．05）；与ALI组比较，P组肺水含量、MPO活性、IL-1β、TNF—α、IL-6含量、HMGB1表达水平降低，α7nAChR表达上调，7d生存率升高（P〈0．05）；与P组比较，P＋α—BGT组肺水含量、MPO活性、IL-1β、TNF-α、IL-6含量、HMGB1表达水平升高，α7nAChR表达下调，7d生存率降低（P〈0．05）。结论肢体缺血预处理抑制炎性反应减轻小鼠内毒素性急性肺损伤的机制与激活α7nAChR有关。
Objective To evaluate the role of α7 nicotinic acetylcholine receptor （α7nAChR） in reduction of endotoxin-induced acute lung injury （ALl） by limb ischemie 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 table： control group （group C） , ALI group, limb isehemie preconditioning group （group P）, α-bungarotoxin （α-BGT） group, and limb ischemic preconditioning ＋ α-BGT group （group P＋a-BGT）. Normal saline 100 μl was intratracheally instilled in group C. In group ALl, lipopolysaccharide 5 mg/kg was intratracheally instilled （in normal saline） to establish the model of endotoxin-induced ALl. In group P, the mice were subjected to 6 cycles of 5-min isehemia 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 ALl 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�
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2016年第6期765-768,共4页
Chinese Journal of Anesthesiology
关键词
受体
烟碱
缺血预处理
呼吸窘迫综合征
成人
炎症
Receptors, nicotinic
Ischemic preconditioning
Respiratory distress syndrome, adult
Inflammation
