低氧致肺动脉平滑肌细胞钙稳态失衡及药物干预研究进展  

Research progress on hypoxia-induced imbalance of calcium homeostasisin pulmonary artery smooth muscle cells and its treatment

作　　者：盖祥云 赵恩麒[1,2] 王金宇 赵悦孚 何彦峰 林鹏程 GAI Xiang-yun;ZHAO En-qi;WANG Jin-yu;ZHAO Yue-fu;HE Yan-feng;LIN Peng-cheng(College of Pharmacy,Qinghai Minzu University,Xining 810007,China;Key Laboratory for Tibet Plateau Phytochemistry of Qinghai Province, Qinghai Minzu University, Xining 810007, China)

机构地区：[1]青海民族大学药学院,青海西宁810007 [2]青海民族大学青海省青藏高原植物化学重点实验室,青海西宁810007

出　　处：《中国药理学通报》2022年第4期492-496,共5页Chinese Pharmacological Bulletin

基　　金：青海省应用基础项目(No 2020-ZJ-703);2019年中国科学院西部之光项目;青海省“昆仑英才·高端创新创业人才”项目;国家自然科学基金项目(No 81860768);青海民族大学青海省青藏高原植物化学重点实验室专项(No 2020-ZJ-Y20)。

摘　　要：慢性缺氧性肺疾病是世界上最常见的致残和死亡原因之一,低氧性肺动脉高压(hypoxic pulmonary hypertension,HPH)是导致肺部血管阻力升高的主要机制。其发病机制复杂,目前的研究尚未能完全阐明。以往研究发现,肺动脉平滑肌细胞内游离钙离子浓度异常升高是肺血管持续收缩和重塑导致HPH发生的主要诱因。通过综合现有文献,对低氧致肺动脉平滑肌细胞钙稳态失衡的作用机制及相关药物研究进行简要总结,发现低氧可通过调控缺氧诱导因子-1、K^(+)、钙库操纵性钙通道、受体操纵性钙通道、钙敏感受体、低氧诱导促有丝分裂因子,诱导肺动脉平滑肌细胞钙稳态失衡。Ca^(2+)可通过与钙调蛋白结合,启动肌动蛋白-肌球蛋白收缩装置,导致肺血管收缩。Ca^(2+)又能够激活PKC/MAPKs和PI3K/Akt/mTOR通路,引发肺血管重构。Chronic hypoxic lung diseases are major causes of disability and mortality worldwide,which are typically aggravated by hypoxic pulmonary hypertension.The pathogenesis of hypoxic pulmonary hypertension is complex,and its mechanism has not been fully elucidated.The previous studies have shown abnormally elevated levels of free Ca2+in the cytoplasm of pulmonary artery smooth muscle cells to be the predominant drivers of pulmonary hypertension,causing continuous contraction and remodeling of the pulmonary vessels.This article briefly summarizes the mechanism of hypoxia-induced imbalance in calcium homeostasis in pulmonary artery smooth muscle cells,together with its related drug research,based on the existing literature.Hypoxia induces an imbalance in calcium homeostasis in pulmonary artery smooth muscle cells by regulating hypoxia-inducible factor-1,K^(+),store-operated calcium channel,receptor-operated calcium channel,the Ca^(2+)-sensing receptor,and hypoxia-induced mitogenic factor.Ca^(2+)can,in turn,activate the actin-myosin contractile mechanism by binding to calmodulin,leading to pulmonary vasoconstriction.Ca2+can also activate PKC/MAPKs and PI3K/Akt/mTOR pathways,leading to pulmonary vascular remodeling.

关 键 词：低氧性肺动脉高压 肺动脉平滑肌细胞 钙稳态 低氧性肺血管收缩 低氧性肺血管重塑 低氧 

分 类 号：R-332[医药卫生] R322.121