ALPHA7 NICOTINE ACETYLCHOLINE RECEPTOR AGONIST PNU-282987 ATTENUATES ACUTE LUNG INJURY IN A CARDIOPULMONARY BYPASS MODEL IN RATS
ALPHA7 NICOTINE ACETYLCHOLINE RECEPTOR AGONIST PNU-282987 ATTENUATES ACUTE LUNG INJURY IN A CARDIOPULMONARY BYPASS MODEL IN RATS
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ALPHA7 尼古丁乙酰胆碱受体激动剂 PNU-282987 可减轻大鼠心肺转流模型中的急性肺损伤
DOI：
10.1097/shk.0000000000000744
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发表时间：
2017-04-01
期刊：
影响因子：
3.1
通讯作者：
Wang, Xiangrui
中科院分区：
文献类型：
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作者：
Ge, Jiaxi;Tian, Jie;Wang, Xiangrui
目的：体外循环（CPB）存在肺缺血再灌注的风险，可导致急性肺损伤（ALI）。α 7烟碱型乙酰胆碱受体（alpha 7 nAChR）参与高迁移率族蛋白1（HMGB 1）的释放，HMGB 1可促进缺血再灌注损伤后的全身炎症反应。然而，alpha 7 nAChR在CPB中的具体作用知之甚少。本研究采用alpha 7 nAChR激动剂PNU-282987和大鼠CPB模型来确定alpha 7 nAChR是否与CPB诱导的肺损伤相关。研究方法：将30只SD大鼠随机分为正常组、假手术组、CPB组、PNU-282987 + CPB组和PNU-282987+假手术组。大鼠在麻醉下进行CPB 60 min。 通过动脉流入给予PNU-282987（4.8 mg/kg）。CPB后2小时，处理血液、支气管肺泡灌洗液（BALF）和肺组织样本用于研究。结果：CPB大鼠肺组织结构损伤明显。CPB组肺组织α 7 nAChR密度显著低于其他各组，而肺水肿、血清和肺组织炎症标志物、BALF蛋白浓度显著高于其他各组。在PNU-282987 + CPB组中，通过所有上述措施，CPB相关效应均显著改善，但与对照组不同。结论：PNU-282987对CPB诱导的ALI具有保护作用，并抑制HMGB 1的释放。
Objective: Cardiopulmonary bypass (CPB) carries a risk of lung ischemia-reperfusion, leading to acute lung injury (ALI). Alpha7 nicotinic acetylcholine receptor (alpha7nAChR) has been implicated in the release of high mobility group box1 (HMGB1), which promotes systemic inflammation in response to ischemia-reperfusion injury. However, the specific role of alpha7nAChR in CPB is poorly understood. This study employed the alpha7nAChR agonist PNU-282987 and a rat model of CPB to determine whether alpha7nAChR was associated with CPB-induced lung damage. Methods: Thirty Sprague–Dawley rats were randomly divided into five groups as follows: normal group, sham group, CPB group, PNU-282987 plus CPB group, and PNU-282987 plus sham group. Rats were subjected to CPB under anesthesia for 60 min. PNU-282987 (4.8 mg/kg) was administered via arterial inflow. Two hours post-CPB, samples of blood, bronchoalveolar lavage fluid (BALF), and lung tissues were processed for investigations. Results: In CPB rats, structural damage in the lung was marked. Density of alpha7nAChR of the lung in the CPB group was significantly less than all other groups, while lung edema, inflammatory markers in serum and lung, protein concentrations in BALF were significantly higher. In the PNU-282987 plus CPB group, by all the above measures the CPB-associated effects were significantly ameliorated but were not identical to the control groups. Conclusion: Our results suggest that PNU-282987 affords protective effect against CPB-induced ALI, and inhibits HMGB1 release.