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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia
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Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia

机译：内毒素血症期间中央毒蕈碱胆碱能调节全身炎症反应

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摘要

TNF has a critical mediator role in inflammation and is an important therapeutic target. We recently discovered that TNF production is regulated by neural signals through the vagus nerve. Activation of this "cholinergic antiinflammatory pathway" inhibits the production of TNF and other cytokines and protects animals from the inflammatory damage caused by endotoxemia and severe sepsis. Here, we describe a role for central muscarinic acetylcholine receptors in the activation of the cholinergic antiinflammatory pathway. Central muscarinic cholinergic activation by muscarine, the M1 receptor agonist McN-A-343, and the M2 receptor antagonist methoctramine inhibited serum TNF levels significantly during endotoxemia. Centrally administered methoctramine stimulated vagus-nerve activity measured by changes in instantaneous heart-rate variability. Blockade of peripheral muscarinic receptors did not abolish antiinflammatory signaling through the vagus nerve, indicating that peripheral muscarinic receptors on immune cells are not required for the cytokine-regulating activities of the cholinergic antiinflammatory pathway. The role of central muscarinic receptors in activating the cholinergic antiinflammatory pathway is of interest for the use of centrally acting muscarinic cholinergic enhancers as antiinflammatory agents.
机译：TNF在炎症中具有关键的介质作用，并且是重要的治疗靶标。我们最近发现，迷走神经通过神经信号调节TNF的产生。这种“胆碱能抗炎途径”的激活抑制了TNF和其他细胞因子的产生，并保护了动物免受内毒素血症和严重败血症引起的炎性损害。在这里，我们描述了中央毒蕈碱乙酰胆碱受体在胆碱能抗炎途径的激活中的作用。毒蕈碱，M1受体激动剂McN-A-343和M2受体拮抗剂甲辛卡明对中毒蕈碱胆碱能的激活在内毒素血症期间显着抑制了血清TNF水平。通过瞬时心率变异性的变化来衡量，中央给药的甲辛曲明刺激了迷走神经活动。外周毒蕈碱受体的阻断并未消除通过迷走神经的抗炎信号，这表明免疫细胞上的外周毒蕈碱受体不是胆碱能抗炎途径的细胞因子调节活性所必需的。中枢毒蕈碱受体在激活胆碱能抗炎途径中的作用对于使用中枢作用的毒蕈碱胆碱能增强剂作为抗炎剂是令人感兴趣的。

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