Accelerated maturation of pulmonary vasculature by VEGF selective delivery system

通过 VEGF 选择性递送系统加速肺血管系统的成熟

• 批准号: 14370399
• 负责人: ENDO Masato
• 金额: $ 6.78万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370399/
• 关键词: VEGF; pulmonary vasculature maturation; gene transfer; ultrasound; selective delivery system; 肺血管; 肺血管成長; plasmid

We performed the animal experiment to establish the method of accelerating pulmonary vascular maturation by selective delivery of Vascular Endothelial Growth Factor (VEGF) to the lung. VEGF (100μg/kg) or saline was administered intravenously to rats. After ultrasound wave (0.5W/cm2, 1MHz) was applied to the left lung for each animal for 15 minutes, lung tissues for both lungs were obtained for the immunological staining and Enzyme-linked Immunosorbent Assay for VEGF. VEGF was detected in lung vasculature in the left lungs more than that in the right lungs in VEGF administered group. The ratio of the number of lung vessels to the number of alveoli was significantly higher in the left lungs than in the right lungs, which reflected the accelerated vascular proliferation in the left lung. We also examined the possibility of VEGF gene transfer to the lung. Lac Z conjugated plasmid 100μg/kg was injected intravenously to rats and followed by ultrasound projection to the left lung for 15 minutes. Lungs and livers were examined by β-gal staining for lac Z at one day and two days after plasmid injection. Although lac Z was not detected in this protocol, selective gene transfer is promising therapy to accelerate pulmonary vascular maturation. In summary, VEGF was selectively delivered to the lung vasculature by ultrasound following intravenous administration. Gene transfer of VEGF is the next step for clinical application of the therapy to accelerate pulmonary vascular maturation.

本研究通过动物实验，建立了选择性肺内输送血管内皮生长因子（VEGF）促进肺血管成熟的方法。VEGF（100μg/kg）或生理盐水经静脉给予大鼠。对每只动物的左肺施加超声波（0.5W/cm ~ 2，1 MHz）15分钟后，取双肺组织进行免疫组化染色和VEGF的酶联免疫吸附试验。VEGF组左肺血管中VEGF表达高于右肺。左肺血管数与肺泡数的比值明显高于右肺，反映了左肺血管增生加快。我们还研究了VEGF基因转移到肺的可能性。大鼠静脉注射Lac Z结合质粒100μg/kg，超声照射左肺15分钟。在质粒注射后第1天和第2天，通过β-gal染色检测肺和肝中的lac Z。虽然在该方案中没有检测到lac Z，但选择性基因转移是有希望的加速肺血管成熟的治疗方法。总之，静脉内给药后，通过超声将VEGF选择性地递送至肺血管系统。VEGF的基因转移是加速肺血管成熟的治疗的临床应用的下一步。