Franquesa M, Alperovich G, Herrero-Fresneda I, Lloberas N, Bolaños N, Fillat C, Rama I, Cruzado J M, Grinyó J M, Torras J
Laboratory of Experimental Nephrology, Department of Medicine, University of Barcelona, L'Hospitalet, Barcelona, Spain.
Gene Ther. 2005 Nov;12(21):1551-8. doi: 10.1038/sj.gt.3302569.
In the early phase of kidney transplantation, the transplanted kidney is exposed to insults like ischemia/reperfusion, which is a leading cause of acute renal failure (ARF). ARF in the context of renal transplantation predisposes the graft to developing chronic damage and to long-term graft loss. Hepatocyte growth factor (HGF) has been suggested to support the intrinsic ability of the kidney to regenerate in response to injury by its morphogenic, mitogenic, motogenic and antiapoptotic activities. In the present paper, we examine whether human HGF (hHGF) gene electrotransfer helps in the recovery from ARF in a model of rat renal warm ischemia. We also assess the advantages of this form of gene therapy by direct electroporation of the kidney, given that transplantation offers the possibility of manipulating the organ in vivo. We have compared the therapeutic efficiency of two electroporation methodologies in a rat ARF model. Although they both targeted the same organ, the two methods were applied to different parts of the animal: muscle and kidney. Kidney direct electrotransfer was shown to be more efficient not only in pharmacokinetic but also in therapeutic terms, so it may become a clinically practical alternative in renal transplantation.
在肾移植的早期阶段，移植肾会受到诸如缺血/再灌注等损伤，这是急性肾衰竭（ARF）的主要原因。肾移植背景下的急性肾衰竭会使移植物易于发生慢性损伤并导致长期移植物丢失。肝细胞生长因子（HGF）因其形态发生、促有丝分裂、促运动和抗凋亡活性，被认为有助于肾脏在受到损伤时恢复其内在的再生能力。在本文中，我们研究了人肝细胞生长因子（hHGF）基因电穿孔是否有助于大鼠肾热缺血模型中急性肾衰竭的恢复。鉴于移植提供了在体内操纵器官的可能性，我们还通过对肾脏进行直接电穿孔来评估这种基因治疗形式的优势。我们在大鼠急性肾衰竭模型中比较了两种电穿孔方法的治疗效果。尽管两种方法都针对同一器官，但应用于动物的不同部位：肌肉和肾脏。结果表明，肾脏直接电穿孔不仅在药代动力学方面，而且在治疗方面都更有效，因此它可能成为肾移植中一种临床实用的替代方法。
