Question

跪求，请高手翻译。急，急，急！不胜感激。

Etanercept prevents airway hyperresponsiveness by protecting neuronal M2 muscarinic receptors in antigen-challenged guinea pigs

Summary
Background and purpose: Increased tumour necrosis factor- (TNF-) is associated with airway hyperreactivity in antigen-challenged animals. In human asthmatics, TNF- is increased and blocking it prevents airway hyperreactivity in some asthmatic patients. However, the mechanisms by which TNF- mediates hyperreactivity are unknown. Airway hyperreactivity can be caused by dysfunction of neuronal M2 muscarinic receptors that normally limit acetylcholine release from parasympathetic nerves. Here we test whether blocking TNF- receptors with etanercept prevents M2 receptor dysfunction and airway hyperreactivity in antigen-challenged guinea pigs.
Experimental approach: Ovalbumin-sensitized guinea pigs were challenged by inhalation of antigen. Some animals received etanercept (3 mg kg−1 i.p.) 3 h before challenge. 24 h after challenge, airway hyperreactivity and M2 receptor function were tested. Inflammatory cells in bronchoalveolar lavage, blood and lung were counted. TNF- and its receptors were detected by real-time RT-PCR and immunocytochemistry in parasympathetic nerves from humans and guinea pigs and in human neuroblastoma cells.
Key results: Antigen-challenged animals were hyperreactive to vagal stimulation and neuronal M2 receptors were dysfunctional. Both M2 receptor dysfunction and airway hyperreactivity were prevented by etanercept. Etanercept reduced eosinophils around airway nerves, and in blood, bronchoalveolar lavage and airway smooth muscle. Also, TNF- decreased M2 receptor mRNA in human and guinea pig parasympathetic neurons.
Conclusions and implications: Tumour necrosis factor- may contribute to M2 receptor dysfunction and airway hyperreactivity directly by decreasing receptor expression and indirectly by promoting recruitment of eosinophils, containing major basic protein, an M2 antagonist. This suggests that etanercept may be beneficial in treatment of allergic asthma.

Answer 1

依那西普防止气道高反应性，保护神经元M2胆碱受体的抗原挑战豚鼠

摘要
背景及目的：提高肿瘤坏死因子肿瘤坏死因子（ TNF -  ）与气道高反应性的抗原质疑动物。在人类哮喘，肿瘤坏死因子- 是增加和阻止它兄脊可以防止气道高反应性在某些哮喘患者。然而，机制，肿瘤坏死因子- 调解过度反应不明。气道高反应性可能是由神经功能障碍的M2胆碱受体通常限制交感神经释放乙酰胆碱的神经。在这里，我们测试是否阻止肿瘤坏死因子受体与依那西普防止M2受体功能障碍和气道高反应性的抗原挑战豚鼠。
实验方法：卵蛋白致敏豚鼠挑战吸入抗原。一些动物收到依那西普（ 3毫克公斤- 1的IP ） 3小时前的挑战。 24 h后的挑战，气道高反应性和M2受体的功能进行了测试。炎性细胞在支气管肺泡灌洗，血液和肺部计数。羡乎渗肿瘤坏死因子- 及其受体检测的实时RT - PCR和免疫细胞化学的副神经人类和豚鼠和在人类神经母细胞瘤细胞。
主要成果：抗原挑战动物，以刺激迷走神经和神经平方米受体功能失调。双方M2受体功能障碍与气道高反应性被阻止的依那西普。依那西普减少气道嗜酸性粒细胞周围的神经，并在血液，支气管肺泡灌洗和气道平滑肌。此外，肿瘤坏死因子- 降低M2受体mRNA的人力和豚鼠交感神经元。
结论和问题：肿瘤坏死因子可能有助于M2受体功能障碍与气道高反应性下降的直接和间接受体的表达，促进招募嗜酸性粒细胞，其中主要的碱性蛋白，一平方米拮抗剂顷颤。这表明，依那西普可能有利于治疗过敏性哮喘。