Division of Clinical Pharmacology, Department of Diagnostic Services, School of Medicine, University of Modena and Reggio Emilia, Largo del Pozzo 71, 41100 Modena, Italy.
Eur J Pharmacol. 2012 Mar 15;679(1-3):1-8. doi: 10.1016/j.ejphar.2012.01.004. Epub 2012 Jan 24.
Together with undernutrition and, on the opposite, overeating and obesity, sudden tissue hypoperfusion is the most important cause of mortality and disability worldwide. Tissue hypoperfusion/hypoxia rapidly triggers an unrestrained inflammatory cascade that is the main responsible for the severity of the eventual outcome. The brain plays a key role in inflammation, either through activation of the hypothalamic-pituitary-adrenal humoral response or through activation of the vagal "cholinergic anti-inflammatory pathway". Both humoral and nervous brain responses to inflammation are under the regulatory control of melanocortins, which have moreover a direct anti-inflammatory effect on inflammatory cells. Abundant experimental and clinical evidence indicates that MC(3)/MC(4) melanocortin receptor agonists and cholinergic receptor agonists (mainly at the α7-nicotinic subtype) should by now be considered as completely innovative, effective drugs for the treatment of hypoxic conditions; melanocortin agonists being practically devoid of harmful side effects.
与营养不良相反，暴饮暴食和肥胖也是全球范围内导致死亡和残疾的最重要原因。组织低灌注/缺氧会迅速引发不受控制的炎症级联反应，这是最终结果严重程度的主要原因。大脑在炎症中起着关键作用，它可以通过激活下丘脑-垂体-肾上腺体液反应，或者通过激活迷走神经的“胆碱能抗炎途径”来实现。大脑对炎症的体液和神经反应都受到黑皮质素的调节控制，黑皮质素对炎症细胞具有直接的抗炎作用。大量的实验和临床证据表明，MC(3)/MC(4) 黑色素皮质素受体激动剂和胆碱能受体激动剂（主要是α7-烟碱型）现在应该被视为治疗缺氧情况的全新、有效的药物；黑色素皮质素激动剂实际上没有有害的副作用。
