褪黑素与妊娠期高血压疾病的关系研究进展

Research progress on the association between melatonin and hypertensive disorder complicating pregnancy

褪黑素(N-乙酰基-5-甲氧基色胺)为多效性神经内分泌脂溶性小分子物质,主要由松果体分泌。妊娠期间,孕妇夜间褪黑素水平随着妊娠期的进展而升高,产后恢复正常。妊娠期高血压疾病病因复杂,越来越多的证据表明褪黑素参与妊娠期高血压疾病的调控,该调控与褪黑素表达水平、分泌节律和受体水平存在相关性。胎盘血液循环灌注异常、缺血缺氧和孕妇全身血管内皮功能障碍是妊娠期高血压疾病的主要病理生理过程。褪黑素通过直接抗氧化作用,改善线粒体功能障碍和保护滋养层细胞免受氧化损伤,参与胎盘氧化应激水平调控,在防止胎盘缺氧缺血再灌注引起的氧化损伤中发挥保护作用,从而维持胎盘功能稳态。此外,也有证据显示褪黑素通过减少促炎细胞因子以及血管活性化合物的产生和分泌来保护母体血管内皮免受氧化应激损伤,参与孕妇全身血压的调控。这些发现均提示褪黑素可通过氧化应激的调控参与妊娠期胎盘和全身血管功能稳态的维持。该文以褪黑素对妊娠期高血压疾病的影响及相关机制为切入点进行综述,总结了褪黑素在妊娠期高血压疾病发病进程中所发挥的积极作用。

Melatonin(N-acetyl-5-methoxytryptamine)is a polypotent neuroendocrine lipid-soluble small molecule secreted mainly by the pineal gland.During gestation,melatonin levels in the mother at night rise as the pregnancy progresses and return to normal after delivery.The etiology of hypertensive disorder complicating pregnancy(HDCP)is multifaceted.An increasing number of evidence suggests the involvement of melatonin in the pathogenic process,and the regulation is related to its expression level,secretion rhythm and receptor level.Abnormal placental blood circulation,ischemia and hypoxia and systemic vascular endothelium dysfunction are the main pathological processes of HDCP.Through direct antioxidant effect,melatonin improves mitochondrial dysfunction and protects trophoblast cells from oxidative damage,thus participating in the regulation of placental oxidative stress level,and plays a protective role in preventing oxidative damage caused by hypoxic ischemia reperfusion of placenta,thus maintaining placental functional homeostasis.In addition,there is also evidence that melatonin can protect maternal vascular endothelium from oxidative stress by reducing the production and secretion of pro-inflammatory cytokines and vasoactive compounds,and participating in the regulation of systemic blood pressure in pregnant women.These confidences suggest that melatonin can be involved in the maintenance of placental and systemic vascular functional homeostasis during pregnancy through the regulation of oxidative stress.In this article,the effects of melatonin on HDCP and the related mechanisms are reviewed,and the positive role of melatonin in the pathogenesis of HDCP is summarized.