Activation of nicotinic cholinergic receptors prevents ventilator-induced lung injury in rats.
Activation of nicotinic cholinergic receptors prevents ventilator-induced lung injury in rats.
复制标题
DOI：
10.1371/journal.pone.0022386
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Steinberg JG
中科院分区：
文献类型：
--
作者：
Brégeon F;Xeridat F;Andreotti N;Lepidi H;Delpierre S;Roch A;Ravailhe S;Jammes Y;Steinberg JG
呼吸窘迫综合征导致40%到60%的死亡。约10%的超额死亡率可能是由于生命支持机械通风拉伸肺而造成的额外肺损伤和炎症。最近在体外研究表明，α7尼古丁受体(α7-nAChR)的药理激活可以下调参与肺细胞对拉伸反应的炎症反应的细胞内介质。我们的目的是在体内测试α7-nAChR的药理激活对呼吸机诱导的肺损伤(VILI)的保护作用。将麻醉大鼠随机分为4组，分别给予生理盐水或α7-nAChR的特异性激动剂(PNU-282987)，或给予双侧迷走神经电刺激，同时给予或不给予α7-nAChR拮抗剂。常规每搏通气量为10mL/kg的对照组提供了参考数据。生理指标(呼吸系统顺应性、肺重量、血氧分压、动脉压)和肺组织炎症介质含量(IL-6测定采用ELISA法，P物质测定采用高效液相色谱法)均严重受损(假手术组)。迷走神经刺激能够维持接近对照组的呼吸参数，并减轻肺部炎症，但与尼古丁受体阻断相关，提示α7-nAChR参与了迷走神经介导的对VILI的保护作用。PNU-282987可显著降低肺损伤及肺组织IL-6和P物质含量，几乎不影响血浆IL-6水平的升高。肺部病理检查证实了观察到的两组之间的生理差异。以上结果提示，刺激α7-nAChR可减轻大鼠VILI。
Respiratory distress syndrome is responsible for 40 to 60 percent mortality. An over mortality of about 10 percent could result from additional lung injury and inflammation due to the life-support mechanical ventilation, which stretches the lung. It has been recently demonstrated, in vitro, that pharmacological activation of the alpha 7 nicotinic receptors (α7-nAChR) could down regulate intracellular mediators involved in lung cell inflammatory response to stretch. Our aim was to test in vivo the protective effect of the pharmacological activation of the α7-nAChR against ventilator-induced lung injury (VILI). Anesthetized rats were ventilated for two hours with a high stretch ventilation mode delivering a stroke volume large enough to generate 25-cmH2O airway pressure, and randomly assigned to four groups: pretreated with parenteral injection of saline or specific agonist of the α7-nAChR (PNU-282987), or submitted to bilateral vagus nerve electrostimulation while pre-treated or not with the α7-nAChR antagonist methyllycaconitine (MLA). Controls ventilated with a conventional stroke volume of 10 mL/kg gave reference data. Physiological indices (compliance of the respiratory system, lung weight, blood oxygenation, arterial blood pressure) and lung contents of inflammatory mediators (IL-6 measured by ELISA, substance P assessed using HPLC) were severely impaired after two hours of high stretch ventilation (sham group). Vagal stimulation was able to maintain the respiratory parameters close to those obtained in Controls and reduced lung inflammation except when associated to nicotinic receptor blockade (MLA), suggesting the involvement of α7-nAChR in vagally-mediated protection against VILI. Pharmacological pre-treatment with PNU-282987 strongly decreased lung injury and lung IL-6 and substance P contents, and nearly abolished the increase in plasmatic IL-6 levels. Pathological examination of the lungs confirmed the physiological differences observed between the groups. In conclusion, these data suggest that the stimulation of α7-nAChR is able to attenuate VILI in rats.
登录
查看更多内容
影响因子：
56.9
作者：
LOTZ, M;VAUGHAN, JH;CARSON, DA
通讯作者：
CARSON, DA
影响因子：
2.5
作者：
Li, Yi-Fan;LaCroix, Carly;Freeling, Jessica
通讯作者：
Freeling, Jessica
DOI：
10.1073/pnas.0600506103
发表时间：
2006-03-28
影响因子：
11.1
作者：
Pavlov, VA;Ochani, M;Tracey, KJ
通讯作者：
Tracey, KJ
DOI：
10.1111/j.1748-1716.1992.tb09272.x
发表时间：
1992-01-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
LOTVALL, J;RABE, K;CHUNG, KF
通讯作者：
CHUNG, KF
影响因子：
3.6
作者：
Hosur, Vishnu;Loring, Ralph H.
通讯作者：
Loring, Ralph H.