EOP调控呼吸的作用机制　　EOP抑制呼吸主要通过降低脑干神经元对二氧化碳的敏感性。延髓腹侧对EOP的作用尤其敏感，这些细胞对脑细胞外液pH和PaCO2的变化敏感，而EOP可降低它们对二氧化碳的反应。在外周，它们作用于颈动脉体的EOP受体，可抑制因缺氧引起的通气增强反应。医学教育网　　通过分段灌注纳洛酮或吗啡的办法，发现EOP通过其纤维投射或通过脑脊液主要作用于低位脑干，包括延髓腹外侧核，导致呼吸抑制 [医学教育网整理发布]。低位脑干是基本呼吸中枢，其中结合臂旁核（NPB）被称为“调整中枢”，EOP受体密集。据实验推测，弓状核释放的EOP兴奋了NPB区的呼吸相关神经元，可导致呼吸抑制。即使常氧下，在去外周化学感受器的成年兔身上，用电刺激或微量注射胞体兴奋剂至NPB，都可使膈神经活动受抑制，一般认为NPB兴奋能切断吸气，使吸气相转入呼气相；其次，孤束核（NTS）是中枢呼吸活动的传出和多种反射传入的中继站，参与呼吸节律的形成和呼吸调控。NTS密集EOP受体和β内啡肽能神经元胞体，低氧下NTS吸气性神经元活动受到抑制，主要由EOP作用引起，EOP可能来自弓状核轴突释放，也可能是局部EOP的作用。另外，一些神经调质（如单胺类物质、腺苷等）也可以调节EOP受体的兴奋性，间接引起呼吸抑制［17，18］。　　近年发现，大部分EOP受体介导的功能通过G蛋白完成信号传导而发生作用［17］，EOP受体与腺苷酸环化酶作用引起细胞内环腺苷酸/环鸟苷酸（cAMP/cGMP）含量变化及神经末梢摄取Ca2+能力降低，从而引起一系列生理效应。　　EOP与机体的各系统、各种功能都有关，作用十分复杂，有关其与呼吸调控详尽的机制尚有待于进一步阐明。医学教育网　　参考文献　　1　Hughes J, Smith TW, Kosterlitz HW, et al. Identification of two related pentapeptides from the brain with potent opiate activity.Nature, 1975,258:577-579.[医学教育网整理发布]　　2　Lord JAH, Waterfield AA, Hughes J, et al. Endogenous opioid peptides:multiple agonists and recepters. Nature, 1977,267:495-499.　　3　Moss IR, Scarpelli EM.β-endorphin:effects on respiratory regulation.Life Sci, 1978,23:1271-1276.　　4　许铁，胡旭初.中枢神经递质和神经调质对低氧通气抑制反应的影响. 生理科学进展, 1992,23:209-213.　　5　Ison GE, Elshowihy RM. Naloxone-induced enhancement of carbon dioxide stimulated respiration.Life Sci, 1982,31:113-118.　　6　Olson EB.Naloxone accelerates the rate of ventilatory acclimitization to hypoxia in awake rats.Life Sci, 1987,41:1105-1111.　　7　许铁，胡旭初. 中枢β内啡肽和5-羟色胺在低氧通气调控中的关系. 生理学报, 1991,43:589-593.　　8　Schaeffer JI, Hadded GG. Ventilatory response to moderate and severe hypoxia in adult dogs:role of endorphins.J Appl Physiol, 1988,65:1383-1388.　　9　Orlowski JP. Cerebrospinal fluid endorphins and the infant apnea syndrome.Pediatrics, 1986,9:301-309.　　10　Wardlaw SL, Stark RI, Daniel S, et al. Effects of hypoxia on β-endorphin and β-lipotropin release in fetal,newborn and maternal sheep.Endocrinology, 1981,108:1710-1715.　　11　Steinbrook RA, Weinberger SE, Carr EB, et al. Endogenous opioids and ventilatory responses to hypoxia in normal humans.Am Rev Respir Dis, 1985,131:588-591.　　12　Kirsh JL, Muro JR, Stansbury DW, et al.Effect of naloxone on maximal exercise performance and control of ventilation in COPD.Chest, 1989,96:761-766.　　13　Simon PM, Alan P, Lahive K, et al. Naloxone does not alter response to hypercapnia or resistive loading in chronic obstructive pulmonary disease.Am Rev Respir Dis, 1989,139:134-138.　　14　Tobin MJ, Jenouri G, Sackner MA. Effect of naloxone on breathing pattern in patients with chronic obstructive pulmonary disease with and without hypercapnia. Respiration, 1983,44:419-424.　　15　Gislason T, Almqvist M, Boman G, et al. Increased CSF opioid activity in sleep apnea syndrome.Chest, 1989,96:250-254.　　16　Ostermeier AM, Roizen MF,Hautkappe M,et al.Three sudden postoperative respiratory arrests associated with epidural opioids in patients with sleep apnea.Anesth Analg, 1997,85:452-460.　　17　Javaheri S,Teppema LJ,Evers JAM.Effects of aminophylline on hypoxemia-induced ventilatory depression in the cat.J Appl Physiol, 1988,65:1837-1843.　　18　Easton PA, Anthonisen NR.Ventilatory response to sustained hypoxia after pretreatment with aminophylline.J Appl Physiol, 1988,64:1445-1450.。