内皮素-1在肺动脉高压发病机制中的研究进展

内皮素-1是一种作用强、持续时间长的血管收缩物质.内皮素-1不仅可作用于肺血管的内皮细胞、平滑肌细胞、成纤维细胞,参与肺动脉高压的发生,还可通过参与炎性反应与免疫、线粒体代谢异常等过程,在肺动脉高压的发病机制中发挥重要作用.     

肺动脉高压发生和发展中的相关因子

肺动脉高压是一种累进性肺血管系统疾病,其特点在于肌性肺动脉和小动脉阻力增加。肺动脉高压的发病机制十分复杂,在肺动脉高压的发生和发展过程中有许多相关因子的参与,现综述肺动脉高压发生和发展过程中的活化T细胞核因子、缺氧诱导因子-1α、骨形成蛋白受体2和Rho激酶4种相关因子的变化及作用。     

肺血管内皮功能紊乱与肺动脉高压

肺动脉高压是以肺血管阻力进行性增加并伴有不可逆的血管重塑为特征的疾病.越来越多的研究表明,肺血管内皮功能紊乱在肺动脉高压形成的起始及发展阶段都起着重要作用.本文就肺血管内皮功能紊乱在肺动脉高压发病机制中的研究进展作一综述.     

炎症在慢性阻塞性肺疾病相关肺动脉高压发病机制中的作用的研究进展

慢性阻塞性肺疾病(COPD)是以气道、肺实质、肺血管慢性炎症为主要特征的慢性肺疾病.肺动脉高压是COPD的主要并发症.近年来新的研究表明,COPD相关肺动脉高压的主要发病机制除缺氧外,炎症介质如白介素16、C反应蛋白、肿瘤坏死因子α、内皮素1等及炎症细胞如中性粒细胞、T淋巴细胞、巨噬细胞、肥大细胞等也起重要作用.     

微小RNA在肺动脉高压发病机制中的研究进展

肺动脉高压是一种致命性疾病,缺氧、炎症、遗传等各种病因导致肺血管重塑、肺动脉压力升高,最终导致右心衰竭,甚至死亡.但目前对肺动脉高压的发病机制并不清楚,尚无治愈肺动脉高压的药物.近年来,微小RNA在许多疾病病理和生理过程中发挥的作用引起了人们的关注,许多研究表明微小RNA有逆转肺血管重塑,从而治愈肺动脉高压的可能.本文就研究较多的微小RNA在肺动脉高压的发病机制,尤其是参与血管重塑的几条通路的研究进展作一综述.     

东莨菪碱联合前列腺素E1治疗慢性肺源性心脏病心力衰竭

慢性肺源性心脏病肺动脉高压的产生与血管收缩、血管壁重建及原位血栓形成有关[1].升高的血管阻力增加右心室负荷,最终导致右心功能衰竭.前列腺素(PG)在肺动脉高压发病过程中起了重要作用.近年研究发现前列腺素E《,1》(PGE《,1》)在肺源性心脏病肺动脉高压和心力衰竭治疗中有较好的疗效.     

内皮素与肺动脉高压

肺动脉高压是心血管疾病发病中的异常病理状态，其确切的发病机制尚不清楚。已知内皮素是一种强烈的血管收缩和促平滑肌细胞增殖因子，并对肺血管有较强的作用，因而可能在肺动脉高压的发病中有重要意义。     

体液调节因素在肺动脉高压发病机制中的作用

多种体液调节因子在肺循环系统的体液调节中发挥作用。在肺动脉高压的发病过程中，血管收缩、舒张因子的活动失去平衡，血管收缩作用处于主导地位，从而导致肺动脉高压。各种形式的肺动脉高压均发生不同程度肺血管结构重塑和肺血管阻力增加，体液调节因素失衡在此病理过程发生中起着举足轻重的作用。因此，恢复体液调节因素的平衡就成为目前肺动脉高压治疗策略的基础。     

体液调节因素在肺动脉高压发病机制中的作用

多种体液调节因子在肺循环系统的体液调节中发挥作用。在肺动脉高压的发病过程中,血管收缩舒张因子的活动失去平衡,血管收缩作用处于主导地位,从而导致肺动脉高压。各种形式的肺动脉高压均发生不同程度肺血管结构重塑和肺血管阻力增加,体液调节因素失衡在此病理过程发生中起着举足轻重的作用。因此,恢复体液调节因素的平衡就成为目前肺动脉高压治疗策略的基础。1　前列环素((prostaglandin I2,PGI2)PGI2 是由内皮细胞产生的一种强力血管扩张因子和血小板聚集抑制因子。重度肺动脉高压患者出现花生四烯酸局部代谢产物 PGI2 和血栓素 …     

川芎嗪对肺心病患者肺动脉高压的影响及其机制探讨

肺动脉高压是慢性阻塞性肺病（COPD）发展至肺心病的关键病理环节,寻找理想的降低肺动脉高压的方法一直是防治COPD、肺心病的重要研究课题.川芎嗪已被证明能有效缓解肺心病患者的肺动脉高压;但其作用机制尚未清楚.本研究拟从保护肺血管内皮细胞、重建血管活性因子平衡的角度,探讨川芎嗪缓解肺心病肺动脉高压的可能机制.     

低氧诱导因子与低氧性肺动脉高压形成机制的相关研究

低氧诱导因子(hypoxia inducible factor-1,HIF-1)是细胞为适应缺氧环境和各种病理刺激所表达的核心调控因子,可调控多种与低氧条件下细胞生存相关靶基因的转录和信号的转导,在低氧性肺动脉高压、白血病、炎症、肿瘤等多种疾病的发生发展过程中起着重要的作用.近年来研究发现,HIF-1与低氧性肺动脉高压形成机制中离子通道的紊乱、血管活性物质的失衡、炎症的加重、肺血管的重塑等密切相关.本文将对低氧诱导因子的结构特征及其与低氧性肺动脉高压形成机制的最新研究概况作一综述.     

The pathobiology of pulmonary hypertension. Endothelium

Dysfunctional endothelial cells have a central and critical role in the initiation and progression of severe pulmonary hypertension. The elucidation of the mechanisms involved in the control of endothelial cell proliferation and cell death in the pulmonary vasculature, therefore, is fundamentally important in the pathogenesis of severe pulmonary hypertension and of great interest for a better understanding of endothelial cell biology. Because the intravascular growth of endothelial cells resulting in tumorlets is unique to severe pulmonary hypertension, this phenomenon can teach researchers about the factors involved in the formation and maintenance of the normal endothelial cell monolayer. Clearly, in severe pulmonary hypertension, the "law of the endothelial cell monolayer" has been broken. The ultimate level of such a control is at the altered gene expression pattern that is conducive to endothelial cell growth and disruption of pulmonary blood flow. Secondary pulmonary hypertension certainly also is associated with proliferated pulmonary endothelial cells and plexiform lesions that are histologically indistinguishable from those in PPH. What is then the difference in the mechanisms of endothelial cell proliferation between primary and secondary pulmonary hypertension? The authors believe that PPH is a disease caused by somatic mutations in key angiogenesis- or apoptosis-related genes such as the TGF-beta receptor-2 and Bax. The loss of these important cell growth control mechanisms allows for the clonal expansion of endothelial cells from a single cell that has acquired a selective growth advantage. On the other hand, the proliferated endothelial cells in secondary pulmonary hypertension are polyclonal. It follows from this finding that local (vascular) factor(s) (such as increased shear stress), rather than mutations, play a major role in triggering endothelial cell proliferation. In PPH and secondary pulmonary hypertension, the researcher can postulate that the pulmonary vascular bed contains progenitor-like cells with the capacity of dysregulated growth. The main difference in the pathogenesis of primary and secondary pulmonary endothelial cell proliferation therefore may be the initial mechanism involved in the recruitment of an endothelial progenitor-like cell. In PPH, anorexigen-associated, and familial PPH, the proliferation of endothelial cells occurs from a mutated single cell, whereas in secondary pulmonary hypertension, several progenitor-like cells would be activated to grow. The abnormal endothelial cells in both forms of severe pulmonary hypertension expand because of the expression of angiogenesis-related molecules such as VEGF, VEGFR-2, HIF-1 alpha, and HIF-beta. Also important for the expansion of these cells is the down-regulation of expression of apoptosis-related mediators such as TGF-beta receptor-2 or Bax. The success of any therapy for severe pulmonary hypertension requires that the underlying process of endothelial cell proliferation could be controlled or reversed.     

Disorders of thrombocyte function and/or endothelial cell damage as a cause of primary pulmonary hypertension?

The pathophysiology of pulmonary hypertension is, in many cases, unclear and this is true especially for patients with dietary pulmonary hypertension. This paper discusses the hypothesis that platelets, directly or through their interaction with the pulmonary endothelial cell, are involved in the development of pulmonary hypertension. Platelets release vasoactive substances during aggregation or activation and these substances lead to pulmonary vasoconstriction and pulmonary hypertension. The primary target of the activated platelets could be the endothelial cell which has also been demonstrated in animal experiments with crotalaria-induced pulmonary hypertension. Changes in thromboxane--platelets and prostacyclin--endothelial cell interactions could be the basic mechanism responsible for endothelial proliferation and pulmonary vasoconstriction. It has not been ascertained, however, whether the activation of platelets or endothelial dysfunction is the primary lesion. In various animal experiments, changes in platelet function and endothelial damage, as well, have been shown to be initiated by exogenous influences. The investigation of platelets or endothelial cell function in patients with pulmonary hypertension showed evidence of platelet activation but not platelet hyperreactivity. An impaired fibrinolytic activity, which was found in the majority of these patients, was regarded as indicative of endothelial dysfunction. An interference in the physiological interaction of circulating platelets and endothelial cells in the lung with resulting endothelial proliferation and vessel occlusion could well be the initial factor. This process would be self-perpetuating in the development of pulmonary hypertension. An additional example of dietary-induced pulmonary hypertension was observed in patients in Spain after the ingestion of toxic oil.(ABSTRACT TRUNCATED AT 250 WORDS)     

PGE1治疗鱼精蛋白中和肝素诱发肺动脉高压的疗效观察

本研究的目的观察PGE1对鱼精蛋白中和肝素所致肺动脉高压的治疗作用.7例体外循环心内直视手术患者,心内操作结束主动脉根部注射鱼精蛋白对抗肝素后肺动脉平均压≥30mmHg即行PGE1 0.02～0.04蘥*min-1*Kg-1持续输注,并于注射前后不同时间分别监测动脉收缩压(SABP)、舒张压(DABP)、平均动脉压(MABP)、中心静脉压(CVP)、平均肺动脉压(MPAP)、肺毛细血管嵌压(PCWP),采用热稀释法测定心输出量(CO),并计算心指数(CI)、每搏指数(SI)、左心室和右心室做功指数(LVSWI,RVSWI)、肺循环阻力(PVR)及体循环阻力(SVR).结果:PGE1持续输注后,SABP、DABP、CVP、CO、SI未发生变化.肺动脉压、右室做功指数和肺血管阻力在持续PGE1 0.02～0.04μg*min-1*Kg-1注射后30min降低为注射前水平(P＜0.05).结论:持续静脉输注PGE1 0.02～0.04μg*min-1*Kg-1可以逆转体外循环心内直视手术鱼精蛋白中和肝素所致的肺动脉高压,降低肺血管阻力,对动脉压和心排血量无明显影响.     

The effect of sodium oxybutyrate on various regulatory mechanisms of pulmonary hemodynamics in experimental tuberculosis in dogs]

The role of cyclic nucleotides and prostaglandins E1 and F2 alpha in pulmonary hypertension formation was elucidated in experimental tuberculosis in dogs and the mechanism of a hypotensive action of sodium oxybutyrate specified with consideration of its influence on the non-gas exchange pulmonary function. The level of the above compounds was studied in the blood taken from the pulmonary artery and aorta in comparison with pulmonary artery pressure prior to and after intravenous injection of sodium oxybutyrate, an antihypoxant. Pulmonary vessel tone was found to depend on the cGMP content and synthesis in the lungs both in health and in tuberculosis and pulmonary hypertension in tuberculosis was associated with a deranged level and correlation of cAMP, cGMP and prostaglandins E1 and F2 alpha in pulmonary circulation. It has been demonstrated that the hypotensive effect of sodium oxybutyrate is associated with its influence on these biochemical parameters in plasma.     

先心病合并重度肺动脉高压围术期体液因素对肺损伤的影响

目的 :探讨先心病合并重度肺动脉高压围术期体液因素对肺损伤的作用机制。方法 :2 0 0 0年 1月至 2 0 0 1年 2月 ,连续对 31例先天性心脏病室间隔缺损 (非肺动脉高压 16例 ,重度肺动脉高压 15例 )直视修补术患者分组进行临床研究 ,在围术期对血栓素B2 (TXB2 )和 6 酮 前列腺素F1α(6 keto PGF1α)、丙二醛 (MDA)、IL 6、IL 8的变化进行研究 ,并结合体外循环前、后肺动脉压、全肺阻力变化进行分析。结果 :围术期TXB2 、6 keto PGF1α与TXB2 的比值 (P T)、MDA、IL 6、IL 8的变化与围术期肺动脉压、全肺阻力、呼吸指数的改变有着密切相关。结论 :在围术期先心病合并重度肺动脉高压组的体液因素变化较非肺动脉高压患者剧烈 ,易发生肺损伤 ,围术期肺动脉高压危象是肺损伤在血液动力学方面的表现     

钙库操纵性钙通道特性及其与低氧性肺血管收缩、重构的关系

肺动脉平滑肌细胞内Ca2+浓度增加是导致低氧性肺血管收缩与重构的重要分子基础.由瞬时受体电位蛋白构成的钙库操纵性钙通道(store-operated channels,SOC)是调节细胞内Ca2+浓度的重要机制,并参与了肺动脉高压时血管收缩和重构过程.充分了解SOC通道的特性,对深入认识肺动脉高压发病的病理生理学机制、指导临床治疗策略具有重要意义.     

COPD并发肺动脉高压与Rho激酶表达的相关性分析

目的分析老年COPD患者并发肺动脉高压与血清Rho激酶表达的相关性。方法分析我院接受治疗的COPD患者的临床资料。依据患者是否合并肺动脉高压分为观察组、对照组。结果共纳入观察组38例,对照组40例。观察组患者肺动脉平均压、血清ROCK1、单核细胞ROCK1、肿瘤坏死因子α及C-反应蛋白水平均显著高于对照组(P0.001)。观察组患者血清ROCk1水平与肺动脉高压呈现显著性正相关(P0.001)。观察组患者单核细胞ROCk1水平与肺动脉高压呈现显著性正相关(P=0.004)。结论合并肺动脉高压的老年COPD患者,外周血及单核细胞内ROCK1表达均升高,且与肺动脉平均压力呈现正相关。提示ROCK1是干预COPD向肺动脉高压进展的新靶点。     

Endothelin-1 Levels in Interstitial Lung Disease Patients During Sleep

Background: Hypoxemia stimulates endothelin-1 (ET-1) secretion. The reduction in alveolar ventilation during sleep is considered sufficient to account for the hypoxemia observed in patients with respiratory diseases. Objective: The aim of this study was to evaluate the arterial ET-1 levels and their relationship with pulmonary hypertension in patients with interstitial lung disease (ILD) during sleep. Methods: We examined 38 patients with ILD using formal polysomnography (electroencephalogram, electrocardiogram, airflow, respiratory muscle movement, oximeter) to detect the presence of nocturnal, nonapneic, oxyhemoglobin desaturation. All patients desaturated below a baseline sleep saturation of 90% for 5 minutes or more, reaching a nadir saturation of at least 85%. Each patient had already undergone right heart catheterization with a Swan-Ganz catheter for measuring hemodynamic parameters. Sampling of arterial blood from a radial artery line for determination of blood gases and ET-1 values was performed simultaneously, after 5 minutes of the first desaturation. Results: At rest, arterial ET-1 levels were higher in ILD patients (1.73 ± 0.37 mgr/mL) than in controls (1.22 ± 0.15 mgr/mL) (p < 0.001). Also, the patients with pulmonary hypertension (Pa > 20 mm Hg) presented significantly higher arterial ET-1 levels (1.86 ± 0.32 mgr/mL) than those without pulmonary hypertension (1.31 ± 0.13 mgr/mL) (p < 0.001). Arterial ET-1 levels were significantly correlated with mean pulmonary arterial pressure (PAP) (r = 0.749, p < 0.001), and arterial oxygen partial pressure (PaO₂) (r = 0.79, p < 0.001). At sleep, during desaturation, arterial ET-1 levels significantly increased in all patients (2.46 ± 0.13 mgr/mL) as compared with resting values (p < 0.001). Arterial ET-1 levels were significantly correlated with PAP (r = 0.657, p < 0.001) and PaO2 (r = 0.93, p < 0.001). Conclusions: According to our study, arterial ET-1 is markedly increased in ILD patients, especially in those with pulmonary hypertension.