Hepatocyte growth factor improves the survival of rats with pulmonary arterial hypertension via the amelioration of pulmonary hemodynamics.
Hepatocyte growth factor improves the survival of rats with pulmonary arterial hypertension via the amelioration of pulmonary hemodynamics.
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DOI：
10.3892/ijmm.2011.616
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发表时间：
2011-04
影响因子：
5.4
通讯作者：
K. Hiramine;Naoyuki Sata;A. Ido;R. Kamimura;Kentaro Setoyama;Kousuke Arai;N. Nuruki;Yasuhiro Tanaka;H. Uto;H. Tsubouchi
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文献类型：
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作者：
K. Hiramine;Naoyuki Sata;A. Ido;R. Kamimura;Kentaro Setoyama;Kousuke Arai;N. Nuruki;Yasuhiro Tanaka;H. Uto;H. Tsubouchi
肝细胞生长因子（HGF）是一种多功能生长因子，具有促有丝分裂、抗凋亡和抗纤维化活性。在这项研究中，我们研究了重组人肝细胞生长因子对肺动脉高压的影响。通过单次注射野百合碱（MCT）诱导大鼠肺动脉高压，并使用渗透泵将重组人HGF（0.12 mg/天）注入右心室腔，并在MCT注射后21天皮下植入。连续静脉输注重组人HGF 14天可延长患有严重MCT诱导的肺动脉高压的动物的存活时间。虽然推注重组人肝细胞生长因子不影响肺动脉压，14天的重组人肝细胞生长因子的管理衰减的炎性细胞浸润，基质积累和血管中膜增厚。结果，肺腔扩大，肺动脉压显著降低。此外，连续给予重组人HGF抑制肺组织血小板衍生生长因子的表达，这在肺动脉高压的发展中起着重要作用。这些结果表明，重组人肝细胞生长因子可能具有改善肺动脉高压症状和改变临床进程的巨大潜力。
Hepatocyte growth factor (HGF) is a multifunctional growth factor with mitogenic, anti-apoptotic and anti-fibrotic activities. In this study, we investigated the effect of administration of recombinant human HGF on pulmonary arterial hypertension. Pulmonary arterial hypertension was induced in rats by a single injection of monocrotaline (MCT) and recombinant human HGF (0.12 mg/day) was administered into the right ventricle cavity using osmotic pumps, which were implanted subcutaneously 21 days after MCT injection. Continuous intravenous delivery of recombinant human HGF for 14 days led to prolonged survival of animals suffering from severe MCT-induced pulmonary arterial hypertension. Although a bolus injection of recombinant human HGF did not affect pulmonary arterial pressure, a 14-day administration of recombinant human HGF attenuated the inflammatory cell infiltrate, matrix accumulation and vascular medial thickening. As a consequence, the pulmonary lumen was enlarged and the pulmonary arterial pressure was significantly reduced. Additionally, continuous administration of recombinant human HGF suppressed lung tissue expression of platelet-derived growth factor, which plays an important role in the development of pulmonary arterial hypertension. These results indicate that recombinant human HGF possibly has a great potential for improving symptoms and altering the clinical course of pulmonary arterial hypertension.