治疗肺动脉高压药物的研究进展摘要肺动脉高压是一种以肺血管阻力进行性增加和右心功能衰竭为特征的的恶性肺血管疾病，特征性的病理改变为小肺动脉内膜纤维化，中膜肥厚，外膜增生，丛样病变及动脉管腔闭塞。
肺动脉高压对传统的治疗药物反应差，大多数病人在确诊后2~3年死亡。
尽管一些新的药物如前列腺类似物，内皮素受体拮抗剂和磷酸二脂酶5抑制剂已经显示了对重度肺动脉高压病人的血流动力学，运动耐量和生存率具有肯定的作用，但肺动脉高压病人长期的预后仍然不容乐观。
因此，寻找对这种疾病新的治疗方法就具有了非常重要的意义。
在过去的几年中，对肺动脉高压病理生理机制的研究已经取得了很大的进展。
已有证据强烈地提示内皮细胞丢失和内皮功能不全在肺动脉高压的发生和发展中起着十分重要的作用。
改善内皮功能或恢复内源性血管活性物质之间的平衡是目前用来治疗肺动脉高压的有效方法，对内皮功能异常在肺动脉高压形成中作用以及遗传因素如何影响内皮功能的进一步认识，将有助于发展出更新的靶向疗法。
根据已阐明的肺动脉高压发病机制，联合应用针对不同治疗靶点的药物，将成为肺动脉高压更为有效的治疗选择。
一些药物如PDE抑制剂可以提高和延长其它药物如前列环素的作用。
联合治疗的目的在于充分发挥各种药物的作用，最大程度降低不良反应的发生。
目前的联合用药方案往往从伊洛前列素、西地那非及波生坦中任意选择两种或三种联合，目前多数专家推荐PDE-5抑制剂和波生坦的联合，用于患者长期治疗。
肺动脉高压是一种发病机制复杂，预后差的疾病。
近几年在肺动脉高压的诊断和治疗方面取得了很大的进步，随着对药物联合治疗的研究、新药物的开发，肺动脉高压患者的预后将会进一步提高。
关键词肺动脉高压；药物治疗；内皮素；PDE抑制剂Treatment of pulmonary hypertension drugresearchAbstractPulmonary arterial hypertension is a kind of pulmonary vascular resistance progressive increase and right heart function failure for the characteristics of malignant pulmonary vascular disease, characteristic pathological changes for small pulmonary artery intima fibrosis, the membrane hypertrophy and hyperplasia of outer membrane, cluster sample lesions and artery lumen block. Pulmonary artery high pressure to the traditional treatment drug reaction is poor, most patients are diagnosed 2 ~ 3 years after death. Although some new drugs such as prostate analogues, endothelin receptor antagonist and diphosphate lipases 5 inhibitors have shown that the severe pulmonary hypertension patient blood flow dynamics, exercise tolerance and survival rate has certain effect, but pulmonary hypertension patients long-term prognosis is still not optimistic. Therefore, looking for new treatments for the disease has a very important significance. In the past few years, the pulmonary hypertension pathophysiological mechanism research has made great progress. Evidence has been strongly hint endothelial cell loss and endothelial dysfunction in the occurrence and development of pulmonary hypertension plays a very important role.Improve endothelial function or recovery endogenous vascular active material balance is currently used to treat pulmonary arterial hypertension effective method for endothelial dysfunction in the pulmonary artery high pressure formation of function and genetic factors how to affect the further understanding endothelial function, will help to develop newer targeted therapy. According to the already stated pah pathogenesis, the combined use of different treatment drugs that target, will become pulmonary hypertension is moreeffective in the treatment of choice. Some drugs such as PDE inhibitors can improve and extend its it drugs such as the role of the forefront of the ring element. Combination therapy aims to give full play to the role of various drugs, the greatest degree to reduce the occurrence of adverse reactions. The combination regimen often from Iraq's front row element, sildenafil and bosentan select any two or three joint, at present most experts recommend PDE-5 inhibitor and bosentan for patients in the union of the long-term treatment.Pulmonary arterial hypertension is a kind of pathogenesis complex, with poor prognosis of the disease. In recent years in the diagnosis and treatment of pulmonary hypertension has made great progress, along with to the drug combination therapy research, new drug development, the prognosis of patients with pulmonary hypertension will further improve.Keywords Tuberculosis；Recurrence；Drug resistance；Etiology目录摘要 (I)Abstract (II)第1章绪论 (1)1.1 课题背景 (1)1.1.1 疾病简介 (1)1.1.2 疾病分类 (2)1.1.3 发病原因 (2)1.1.4 病理生理 (2)1.2 原发性肺动脉高压概述 (3)1.2.1 病因与发病机制 (3)1.2.2 临床表现 (5)1.2.3 实验室检查 (5)1.2.4 诊断 (6)1.3 原发性肺动脉高压治疗 (6)1.3.1 一般治疗 (6)1.3.2 抗凝治疗 (6)1.3.3 扩血管治疗 (6)1.3.4 手术治疗 (7)1.3.5 细胞移植治疗 (7)1.4 课题研究目的与意义 (8)第2章内皮功能异常与原发性肺动脉高压 (9)2.1 内皮衍生的血管活性因子 (9)2.2 内皮组织与炎症 (10)2.3 内皮功能异常与血液高凝状态 (11)2.4 本章小结 (12)第3章肺动脉高压的药物治疗 (13)3.1 一般药物治疗 (13)3.1.1 钙离子拮抗剂药物治疗 (13)3.1.2 一氧化氮和精氨酸 (15)3.2 新型靶向药物 (15)3.2.1 前列环素类药物 (15)3.2.2 内皮素受体拮抗剂 (17)3.2.3 磷酸二酯酶抑制剂 (22)3.3 联合治疗 (24)3.4 本章小结 (24)结论 (25)致谢 (26)参考文献 (27)第1章绪论1.1课题背景肺动脉高压是各种原因引起的静息状态下右心导管测得的肺动脉平均压（mean pulmonary arterial pressure，mPAP）≥25mmHg的一组临床病理生理综合征。
