摘要
目的:探讨外源性肝细胞生长因子(HGF)基因转染高动力性肺动脉高压家兔后促进侧支肺血管生成、改善肺血流灌注、降低肺动脉压力的可行性。方法:将肺动脉高压兔随机分为对照组、空病毒组和HGF基因转染组;HGF基因转染组经气管内滴入法转染Ad-HGF,对照组和空病毒组分别气管内滴入同体积PBS液和Ade-no-Null;4周后,通过MacLab/8s多功能生理仪行血流动力学检测,通过抗FⅧ+α-SMA抗体免疫荧光双标检测肺小动脉密度、FITC-lectin灌注+抗α-SMA荧光双标记了解肺血管灌注情况。结果:气管内给药4周后,HGF基因治疗组含平滑肌细胞的小动脉密度较肺动脉高压对照组和空病毒组(12.5±2.7)/mm2明显增多(P<0.05);HGF组肺血流灌注获得有效改善,而肺动脉高压对照组和空病毒转染组肺血管仍处于狭窄甚至闭塞状态;HGF治疗组肺动脉平均压明显低于肺动脉高压对照组和空病毒转染组(P<0.05)。结论:肺动脉高压模型动物经气管滴入法转染外源性HGF,可以促进肺侧支血管生成,增加肺灌注并有效降低肺动脉压力。
AIM: To investigate the feasibility of exogenous hepatocyte growth factor(HGF) gene transfection to promote pulmonary collateral angiogenesis,improve pulmonary perfusion and reduce pulmonary artery pressure in the rabbit model of pulmonary artery hypertension(PAH).METHODS: The model rabbits of PAH were randomly divided into control group,empty vector group and HGF gene transfection group.The rabbits in HGF gene transfection group were transfected with Ad-HGF via intratracheal instillation.Pulmonary hemodynamic indicators were monitored in the 4th week after HGF gene transfection.Density of pulmonary vessels was examined with double-labeling immunofluorescence(endothelial cells were labeled with anti-FⅧ and vascular smooth muscle cells were marked with anti-α-SMA).Double-labeling immunofluorescence of FITC-lectin and anti-α-SMA was also performed to evaluate the pulmonary blood perfusion.RESULTS: Four weeks after transfection,the density of pulmonary arterioles of the rabbits in HGF gene transfection group was higher than that in control group and empty vector group(P0.05),which was confirmed by double-labeling immunofluorescence.Pulmonary blood perfusion in HGF group was significantly increased compared with that in the other two groups,in which pulmonary arterial stenosis and occlusion were observed.The mean pulmonary artery pressure in HGF transfection group was much lower than that in control group and empty vector group(P0.05). CONCLUSION: Four weeks after intratracheal adenoviral-mediated HGF gene transfection,pulmonary collateral vessels and pulmonary perfusion increase,and the pulmonary artery pressure is effectively reduced.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2011年第11期2217-2220,2224,共5页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.30571845)
江苏省自然科学基金资助项目(No.BK2007033)
江苏省高校自然科学基金资助项目(No.07KJD310218)
徐州市科技计划项目(No.XM09B072)
关键词
肝细胞生长因子
血管新生
基因治疗
肺动脉高压
Hepatocyte growth factors
Angiogenesis
Gene therapy
Pulmonary artery hypertension