右美托咪定的中枢神经作用机制研究进展

Research progress in the central nervous system mechanism of dexmedetomidine

右美托咪定是一种α_(2)肾上腺素受体激动剂,具有镇静、镇痛、抗焦虑、抗交感神经的作用,目前已经成为临床麻醉和重症监护室广泛应用的药物。相比于麻醉科其他药物,右美托咪定没有明显的呼吸抑制作用且没有明显的血流动力学改变,且与其他麻醉药配伍可明显减少镇静镇痛药物的用量。在临床应用中发现,右美托咪定可以介导可唤醒的镇静效应。传统认为右美托咪定通过α_(2)肾上腺素受体发挥作用,可以发挥降低血压、舒张血管和降低心率的作用,但对于其如何影响脑内神经环路尚不清楚。近年来关于右美托咪定作用机制的研究逐渐增多,证实下丘脑腹外侧视前区(ventrolateral preoptic nucleus,VLPO)、蓝斑核(locus coeruleus,LC)、中脑腹侧被盖区(ventral tegmental area,VTA)等核团参与其介导的镇静作用,背根神经节(dorsal root ganglion,DRG)、颈上神经节(superior cervical ganglion,SCG)参与其介导的镇痛作用,下丘脑视前区(preoptic area,PO)和下丘脑室旁核(paraventricular nucleus,PVN)参与其介导的体温和水电解质平衡的变化,为理解右美托咪定在中枢神经系统的作用机制提供了新的方向。

Dexmedetomidine,which is anα_(2)adrenergic receptor agonist with sedative,analgesic,anxiolytic and anti-sympathetic effects,has become a widely used drug in clinical anesthesia and intensive care unit(ICU).Compared with other drugs in the department of anesthesiology,dexmedetomidine has no obvious respiratory depression and no obvious hemodynamic changes,and can significantly reduce the dosage of sedative and analgesic drugs when combined with other anesthetics.In clinical applications,dexmedetomidine has been found to induce a sedative response that is associated with rapid arousal.Dexmedetomidine is traditionally thought to act throughα_(2)adrenergic receptors to lower blood pressure,dilate blood vessels and lower heart rate,but it is unclear how it affects neural circuits in the brain.In recent years,there has been an increasing number of studies on the mechanism of action of dexmedetomidine,which has confirmed that the ventrolateral preoptic nucleus(VLPO),locus coeruleus(LC)and ventral tegmental area(VTA)of the hypothalamus are involved in the sedation mediated by dexmedetomidine,the dorsal root ganglion(DRG)and superior cervical ganglion(SCG)are involved in dexmedetomidine-mediated analgesia,and the hypothalamic preoptic area(PO)and hypothalamic paraventricular nucleus(PVN)are involved in the changes in body temperature and waterelectrolyte balance mediated by dexmedetomidine,providing a new direction for understanding the mechanism of dexmedetomidine in the central nervous system.