Department of Cardiothoracic Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
J Thorac Cardiovasc Surg. 2013 Jul;146(1):198-205. doi: 10.1016/j.jtcvs.2012.08.056. Epub 2012 Sep 23.
The study objective was to investigate the effect of recombinant human hepatocyte growth factor gene transfection via an endotracheal approach on hyperkinetic pulmonary artery hypertension rabbit models.
The rabbits with established pulmonary artery hypertension were separated into a gene transfection group (rabbits treated with intratracheal instillation of human hepatocyte growth factor 2 × 10(9) plaque-forming units coded by replication-defective recombinant adenovirus), an empty vector group, and a control group. Two weeks after endotracheal gene transfection, immunohistochemistry examination and Western blot were used to detect the protein expression of human hepatocyte growth factor. The hemodynamic data were measured, and pulmonary angiography was performed to investigate the pulmonary collateral vessels. The vascular density in lung also was analyzed.
Two weeks after gene transfection, human hepatocyte growth factor was expressed in the gene transfection group. The mean pulmonary artery pressure in the gene transfection group was lower than in the control and empty vector groups (P < .05 for both). The arteriolar density in the lung tissues of the gene transfection group was higher than in the other groups (P < .05), which was confirmed by immunohistochemistry, double-labeling immunofluorescence, and pulmonary angiography.
Human hepatocyte growth factor was expressed in rabbit lung after gene transfection via an airway approach. Recombinant human hepatocyte growth factor transfection ameliorates the pulmonary artery hypertension induced by shunt flow by promoting angiogenesis in lung tissues.
本研究旨在通过气管内途径转染重组人肝细胞生长因子基因,观察其对高动力性肺动脉高压兔模型的作用。
将建立肺动脉高压的兔模型分为基因转染组(经气管内滴注复制缺陷型重组腺病毒编码的 2×10(9) 噬菌斑形成单位的人肝细胞生长因子)、空载体组和对照组。气管内基因转染 2 周后,采用免疫组化和 Western blot 检测人肝细胞生长因子蛋白的表达。测量血流动力学数据,并进行肺动脉造影以研究肺侧支血管,分析肺血管密度。
基因转染 2 周后,基因转染组可检测到人肝细胞生长因子的表达。与对照组和空载体组相比,基因转染组的平均肺动脉压更低(均 P<.05)。基因转染组肺组织中小动脉密度高于其他组(均 P<.05),免疫组化、双标免疫荧光和肺动脉造影均证实了这一点。
气道途径基因转染可在兔肺内表达人肝细胞生长因子。重组人肝细胞生长因子转染通过促进肺组织血管生成,改善分流所致的肺动脉高压。