Zhang Fengwei, Wu Shuming, Lu Xianshuo, Wang Mo, Liu Meiming
Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, China.
Ann Thorac Surg. 2008 Feb;85(2):581-5. doi: 10.1016/j.athoracsur.2007.08.043.
Nitric oxide, a potent vasodilator with an important role in the regulation of pulmonary vascular tone, is synthesized by a family of nitric oxide synthases. To determine whether endothelial nitric oxide synthase (eNOS) gene transfer may prevent pulmonary hypertension, the effects of transfer of the eNOS gene to the lung were studied in rabbits with pulmonary hypertension induced by high pulmonary blood flow.
Adenoviral vector encoding the eNOS gene was intratracheally transfected into the lung of rabbits with flow-induced pulmonary hypertension. Rabbits instilled intratracheally with adenoviral vector without encoding the eNOS gene served as a control group. Hemodynamic data were recorded before and after transfection, and transgene expression was investigated.
Pulmonary hypertension was significantly attenuated in eNOS gene-transfected rabbits compared with control animals (mean pulmonary arterial pressure, 22.3 +/- 5.5 versus 41.0 +/- 6.9 mm Hg; pulmonary vascular resistance, 326 +/- 42 versus 618 +/- 66 dynes x s x cm(-5); p < 0.01). Systemic arterial pressure and systemic vascular resistance were unaffected. There was an increase in calcium-dependent conversion of L-arginine to L-citrulline in the lung (16.81 +/- 0.72 versus 4.11 +/- 0.41 pmol x mg protein(-1) x h(-1)) and cyclic guanosine monophosphate levels (0.138 +/- 0.015 versus 0.065 +/- 0.003 pmol/mg protein). Immunohistochemical staining showed expression of the eNOS gene was detected mainly in endothelial cells of small pulmonary vessels. Transgene expression was confirmed using Western blot analysis.
These data suggest that intratracheal adenoviral-mediated eNOS gene transfer can attenuate flow-induced pulmonary hypertension in rabbits and may represent a new form of therapy for the treatment of flow-induced pulmonary hypertension.
一氧化氮是一种强效血管舒张剂，在调节肺血管张力方面发挥重要作用，它由一氧化氮合酶家族合成。为了确定内皮型一氧化氮合酶（eNOS）基因转移是否可预防肺动脉高压，我们在高肺血流量诱导的肺动脉高压兔中研究了eNOS基因转移至肺的效果。
将编码eNOS基因的腺病毒载体经气管内转染至血流诱导性肺动脉高压兔的肺中。经气管内滴注不含eNOS基因编码的腺病毒载体的兔作为对照组。在转染前后记录血流动力学数据，并研究转基因表达情况。
与对照动物相比，eNOS基因转染兔的肺动脉高压明显减轻（平均肺动脉压，22.3±5.5对41.0±6.9 mmHg；肺血管阻力，326±42对618±66达因×秒×厘米⁻⁵；p<0.01）。体动脉压和体循环血管阻力未受影响。肺中L-精氨酸向L-瓜氨酸的钙依赖性转化率增加（16.81±0.72对4.11±0.41皮摩尔×毫克蛋白⁻¹×小时⁻¹），环磷酸鸟苷水平升高（0.138±0.015对0.065±0.003皮摩尔/毫克蛋白）。免疫组织化学染色显示eNOS基因表达主要在肺小血管内皮细胞中检测到。使用蛋白质印迹分析证实了转基因表达。
这些数据表明，经气管内腺病毒介导的eNOS基因转移可减轻兔血流诱导性肺动脉高压，可能代表了一种治疗血流诱导性肺动脉高压的新治疗形式。
