改善肺动脉高压中肺血管重构治疗策略的研究进展  

Research progress on therapeutic strategies for improving pulmonary vascular remodeling in pulmonary hypertension

作　　者：盖祥云 赵恩麒 何彦峰 李占强 赵悦孚 王金宇 李丰润 GAI Xiang-yun;ZHAO En-qi;HE Yan-feng;LI Zhan-qiang;ZHAO Yue-fu;WANG Jin-yu;LI Feng-run(School of Pharmacy,Qinghai Minzu University,Xining 810007,China;Key Laboratory for Tibet Plateau Phytochemistry of Qinghai Province,Xining 810007,China;Research Center for High Altitude Medicine,Qinghai University,Xining 810001,China)

机构地区：[1]青海民族大学药学院,青海西宁810007 [2]青海省青藏高原植物化学重点实验室,青海西宁810007 [3]青海大学高原医学研究中心,青海西宁810001

出　　处：《中国药理学通报》2022年第11期1612-1616,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”专项;国家自然科学基金资助项目(No.81860768)。

摘　　要：肺动脉高压(pulmonary hypertension,PH)是一种慢性、进行性、高死亡率的疾病。各类PH具有相同特征:肺动脉内皮细胞和平滑肌细胞的过度增殖、抗凋亡和炎症导致的肺小血管的渐进性增厚,引发肺血管的重构和肺血管阻力增加,最终导致右心室肥厚、心衰、死亡。目前治疗PH的药物(L型钙通道阻滞剂、磷酸二酯酶5抑制剂、鸟苷酸环化酶激活剂、内皮素受体拮抗剂、合成前列环素及其类似物)主要通过松弛肺血管降低肺动脉压,不能根本治愈患者。因此,研发有效改善甚至逆转肺血管重构的药物,是治疗PH的关键。近年来,围绕肺血管重构开展的研究主要有:新的小分子化合物的合成;成熟药物的改造;联合用药及剂型改造等;基于中医“肺胀”等理论,对中药制剂以及中药复方的药效评价;中药单体的研究;新靶点的研究。Pulmonary hypertension(PH)is a chronic,progressive,high-mortality disease characterized by a continuous increase in pulmonary vascular pressure.All types of PH have the same characteristics,i.e.,the excessive proliferation,anti-apoptosis and inflammation of pulmonary artery endothelial cells and smooth muscle cells,which leads to progressive thickening of pulmonary small vessels,resulting in pulmonary vascular remodeling and increased pulmonary vascular resistance,ultimately leading to right ventricular hypertrophy,heart failure,and death.The drugs used to treat PH mainly include L-type calcium channel blockers,phosphodiesterase 5 inhibitors,guanosine cyclase activators,endothelin receptor antagonists,and synthetic prostacyclin and its analogues.These drugs reduce pulmonary artery pressure by relaxing pulmonary blood vessels but do not cure the patient,and their prognosis remains poor.Therefore,the development of drugs that can effectively improve or even reverse pulmonary vascular remodeling is the key to treating PH.In recent years,studies on pulmonary vascular remodeling mainly included(1)the synthesis of new small-molecule compounds;(2)the transformation of mature drugs,such as the use of drug combinations and dosage form transformation,etc.;(3)the pharmacodynamic evaluation of traditional Chinese medicines and derived compounds based on the theory of“lung distension”;(4)research into monomers of traditional Chinese medicine;and(5)research into new targets.

关 键 词：肺动脉高压 肺血管重构 肺动脉平滑肌细胞增殖 化学药物 中药制剂及复方 中药单体 靶点 

分 类 号：R322.121[医药卫生—人体解剖和组织胚胎学] R322.74[医药卫生—基础医学] R544.05R543.20