Protective role of protein C inhibitor in monocrotaline-induced pulmonary hypertension
Protective role of protein C inhibitor in monocrotaline-induced pulmonary hypertension
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DOI：
10.1111/j.1538-7836.2006.02174.x
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发表时间：
2006-11-01
影响因子：
10.4
通讯作者：
Taguchi, O.
中科院分区：
文献类型：
--
作者：
Nishii, Y.;Gabazza, E. C.;Taguchi, O.
背景资料：蛋白C抑制剂（PCI）在受精、凝血、纤溶和激肽系统等多种生物学过程中发挥作用。目的：我们假设PCI参与肺动脉高压的发病机制。为了证明这一点，我们比较了肺中过表达PCI的小鼠与野生型（WT）小鼠肺动脉高压的发展。通过皮下注射诱导肺动脉高压。每周注射600 mg kg（-1）野百合碱，持续8周。结果如下：野百合碱处理的野生型小鼠的右心室动脉压显着增加与野百合碱处理的转基因小鼠相比。与单百合碱处理的PCI转基因小鼠相比，单百合碱处理的WT小鼠支气管肺泡灌洗液（BALF）中凝血酶-抗凝血酶复合物、单核细胞趋化蛋白-1和血小板衍生生长因子的水平以及肿瘤坏死因子-α的血浆水平显著升高。与生理盐水处理的PCI转基因小鼠相比，检测到从野百合碱处理的PCI转基因小鼠的BALF中PCI-凝血酶复合物的水平增加。结论：这项研究表明，PCI在肺中的表达增加对野百合碱诱导的肺动脉高压具有保护作用，表明PCI对治疗这种疾病具有潜在的有益作用。
Background: Protein C inhibitor (PCI) plays a role in multiple biological processes including fertilization, coagulation, fibrinolysis and kinin systems. Objectives: We hypothesized that PCI participates in the pathogenesis of pulmonary hypertension. To demonstrate this, we compared the development of pulmonary hypertension in mice overexpressing PCI in the lung with wild-type (WT) mice. Pulmonary hypertension was induced by s.c. injection of 600 mg kg(-1) of monocrotaline weekly for 8 weeks. Results: Right ventricular arterial pressure was significantly increased in monocrotaline-treated WT mice compared with that in monocrotaline-treated transgenic mice. Bronchoalveolar lavage fluid (BALF) levels of thrombin-antithrombin complex, monocyte chemoattractant protein-1 and platelet-derived growth factor, and the plasma level of tumor necrosis factor-alpha were significantly increased in monocrotaline-treated WT mice as compared with monocrotaline-treated PCI transgenic mice. Increased level of PCI-thrombin complex was detected in BALF from monocrotaline-treated PCI transgenic mice as compared with saline-treated PCI transgenic mice. Conclusions: This study showed that increased expression of PCI in the lung is protective against monocrotaline-induced pulmonary hypertension, suggesting a potential beneficial effect of PCI for the therapy of this disease.