血红素加氧酶1与子痫前期发病机制的研究进展

Relationship between HO-1 and the Pathogenesis of Pre-eclampsia

子痫前期是妊娠期最常见的疾病之一,其不仅能导致胎盘早剥、妊娠妇女肝肾功能受损、早产、胎儿生长受限等,也是孕产妇及围生儿死亡的常见原因,由于其严重危害母儿健康,其发病机制一直是产科领域的研究热点。子宫螺旋动脉重塑障碍、血管内皮受损、遗传、免疫失衡及炎症反应等与子痫前期关系密切,其中广泛的血管内皮受损是该病发生的关键环节。近年研究发现,氧化应激及可溶性血管内皮因子(s Eng)、可溶性血管内皮生长因子受体1(s Flt-1)升高是导致血管内皮受损的主要原因,而血红素加氧酶1(HO-1)是一种可诱导的抗氧化酶,HO-1及其催化代谢产物一氧化碳(CO)、胆红素不仅对正常妊娠的胎盘形成、胎盘功能的维持及胎儿的生长发育具有重要保护作用,还能通过激活胎盘保护型信号通路、合成还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)还原酶来抑制子痫前期妇女体内的氧化应激以及通过降低血管内皮损伤因子如s Eng、s Flt-1对血管内皮的损害、促进血管内皮保护因子如血管内皮生长因子(VEGF)对血管的保护作用来抑制子痫前期的发生,推测HO-1及其催化代谢产物能够为子痫前期预防及治疗带来新的突破。

Pre-eclampsia is one of the most common complication in pregnancy, it can not only lead to placental abruption, maternal liver and kidney damage, premature delivery, fetal growth restriction, etc., but also is the most common cause of maternal and perinatal mortality. Because of its serious harm to mother and child health, its pathogenesis has long been a hot issue of obstetrical research. Uterine spiral artery remodeling disorders, vascular endothelial damage, genetic, immune imbalance and inflammatory responses are related to the pre-eclampsia. Among these factors, a wide range damage of vascular endothelial cells is regarded as the key pathological mechanisms in the development of pre-eclampsia. Recent studies have proved that vascular endothelial damage is mainly caused by oxidative stress and the increased level of soluble endoglin（s Eng）, soluble vascular endothelial growth factor receptor 1（s Flt-1）. However, we found that heme oxygenase-1（HO-1）, an inducible antioxidant enzyme, along with its metabolites such as carbon monoxide（CO）, bilirubin can not only play an important role in normal pregnancy by maintaining placental function,promoting the development of placenta and fetal growth, but also has significant function in suppressing the occurrence of preeclampsia by reducing oxidative stress through activating the protective signaling pathways, increasing NADPH level and by protecting endothelial vascular function through reducing endothelial injury factors such as s Eng, s Flt-1, promoting endothelial protective factor such as VEGF. Therefore, we expected that HO-1 and its metabolites can bring new breakthroughs in the prevention and treatment of pre-eclampsia.