Granulocyte colony-stimulating factor prevents progression of monocrotaline-induced pulmonary arterial hypertension in rats
Granulocyte colony-stimulating factor prevents progression of monocrotaline-induced pulmonary arterial hypertension in rats
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DOI：
10.1253/circj.71.138
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发表时间：
2007-01-01
影响因子：
3.3
通讯作者：
Yamaguchi, Iwao
中科院分区：
文献类型：
--
作者：
Maruyama, Hidekazu;Watanabe, Shigeyuki;Yamaguchi, Iwao
背景肺微血管再生并用功能性内皮细胞替代肺动脉病变可能是治疗晚期肺动脉高压（PAH）的一种新型有效的治疗策略。在本研究中，据推测，粒细胞集落刺激因子（G-CFS），诱导内皮细胞的增殖，将刺激内皮再生原位受损的肺血管系统的网站，并防止发展的PAH.Methods和结果的G-CSF每日给药48天不影响正常Fischer 344大鼠的血液动力学。用野百合碱（60 mg/kg）诱导PAH，并每天给予G-CSF（100 μ g/kg/天）。超声心动图结果和侵入性导管研究表明，给予G-CSF的大鼠PAH进展显著减少。此外，G-CSF增加肺动脉的Ki-67阳性PAH大鼠，但不加速c-kit阳性细胞募集到外周血。每日剂量的G-CSF在2和100 μ g/kg.Conclusions的PAH rates. Conclusions的生存和体重增加改善PAH的进展在大鼠模型中，可能是通过刺激肺内皮细胞增殖受损的肺血管的网站。这些结果表明，基于血管再生的概念，PAH的细胞因子治疗是有效的。
Background Regeneration of the lung microvasculature and replacing pulmonary artery lesions with functional endothelial cells could be a novel and effective therapeutic strategy for treating advanced pulmonary arterial hypertension (PAH). In the present study it was postulated that granulocyte colony-stimulating factor (G-CFS), which induces the proliferation of endothelial cells, would stimulate endothelial regeneration in situ at sites of impaired lung vasculature and prevent the development of PAH.Methods and Results Daily administration of G-CSF for 48 days did not affect the hemodynamism of normal Fischer 344 rats. PAH was induced with monocrotaline (60mg/kg) and G-CSF was administered daily (100 mu g/kg per day). Echocardiographic findings and an invasive catheter study indicated a significant decrease in the progression of PAH in rats given G-CSF. Furthermore, G-CSF increased Ki-67 positivity in the pulmonary arteries of PAH rats but did not accelerate c-kit positive cell recruitment into peripheral, blood. Daily doses of G-CSF at both 2 and 100 mu g/kg improved the survival and body weight gain of PAH rats.Conclusions G-CSF improved the progression of PAH in a rat model, possibly by stimulating pulmonary endothelial cells to proliferate at sites of impaired lung vasculature. These findings show that cytokine therapy for PAH is valid based on the concept of vascular regeneration.