Yano M, Mora B N, Ritter J M, Scheule R K, Yew N S, Mohanakumar T, Patterson G A
Division of Cardiothoracic Surgery and the Departmentof Surgery, Department of Pathology, Washington University Schoolof Medicine, St Louis, MO, USA.
J Thorac Cardiovasc Surg. 1999 Apr;117(4):705-13. doi: 10.1016/s0022-5223(99)70290-4.
Proximal pulmonary artery segment transfection may provide beneficial downstream effects on the whole-lung graft. In this study, transforming growth factor-beta1 was transfected to proximal pulmonary artery segments, and the efficacy of transforming growth factor-beta1 transfection was examined in ischemia-reperfusion injury and acute rejection models of rat lung transplantation.
In the ischemia-reperfusion injury model, orthotopic left lung transplantation was performed in F344 rats. In group I, the PPAS was isolated and injected with saline solution. In 2 other groups, lipid67:DOPE:sense (group II) or antisense transforming growth factor-beta1pDNA construct (group III) was injected instead of saline solution. After cold preservation at 4 degrees C for 18 hours, lung grafts were implanted. Graft function was assessed 24 hours later. In the acute rejection model, donor lung grafts were harvested. Proximal pulmonary artery segments were injected with saline solution (group I) or sense (group II) or antisense lipid gene construct (group III) and then implanted. Graft function was assessed on postoperative day 5.
In the ischemia-reperfusion injury study, there were no significant differences in oxygenation, wet-to-dry weight ratios, graft myeloperoxidase activity, or transforming growth factor-beta1 levels in platelet-poor serum or proximal pulmonary artery segment homogenates. In the acute rejection study, oxygenation was significantly improved in group II receiving transforming growth factor-beta1 (group II vs I and III, 136.0 +/- 32.5 vs 54.0 +/- 9.6 mm Hg and 53.8 +/- 14.8 mm Hg; P =.016 and.016). There were no significant pathologic differences. Transforming growth factor-beta1 concentrations from proximal pulmonary artery segment homogenates in group II were significantly higher compared with controls.
Ex vivo transfection of transforming growth factor-beta1 to proximal pulmonary artery segments did not affect reperfusion injury of lung isografts. In acute rejection, however, ex vivo transfection of transforming growth factor-beta 1 to proximal pulmonary artery segments improved allograft function. This suggests that transfection to proximal pulmonary artery segments exerts beneficial downstream effects on the whole-lung allograft.
肺动脉近端节段转染可能对全肺移植物产生有益的下游效应。在本研究中，将转化生长因子-β1转染至肺动脉近端节段，并在大鼠肺移植的缺血再灌注损伤和急性排斥反应模型中检测转化生长因子-β1转染的效果。
在缺血再灌注损伤模型中，对F344大鼠进行原位左肺移植。在I组中，分离肺动脉近端节段并注射生理盐水。在另外2组中，分别注射脂质67:DOPE:正义链（II组）或反义转化生长因子-β1 pDNA构建体（III组）以替代生理盐水。在4℃冷保存18小时后，植入肺移植物。24小时后评估移植物功能。在急性排斥反应模型中，获取供体肺移植物。肺动脉近端节段注射生理盐水（I组）或正义链（II组）或反义脂质基因构建体（III组），然后植入。在术后第5天评估移植物功能。
在缺血再灌注损伤研究中，在氧合、湿干重比、移植物髓过氧化物酶活性或血小板贫血清或肺动脉近端节段匀浆中的转化生长因子-β1水平方面，各组间无显著差异。在急性排斥反应研究中，接受转化生长因子-β1的II组氧合显著改善（II组与I组和III组相比，分别为136.0±32.5 vs 54.0±9.6 mmHg和53.8±14.8 mmHg；P = 0.016和0.016）。病理方面无显著差异。II组肺动脉近端节段匀浆中的转化生长因子-β1浓度与对照组相比显著更高。
将转化生长因子-β1体外转染至肺动脉近端节段不影响同种异体肺移植物的再灌注损伤。然而，在急性排斥反应中，将转化生长因子-β1体外转染至肺动脉近端节段可改善同种异体移植物功能。这表明转染至肺动脉近端节段对全肺同种异体移植物产生有益的下游效应。
