Chen Xing, Chen Zhi, Wang Hanbin, Xiong Xishan, Liu Xiaoling, Hu Chunsheng, Han Yuan, Lu Yuxin, Wu Zuze, Zhang Qinglin
Chinese PLA General Hospital & Chinese PLA Postgraduate Medical School, Beijing 100853, China.
Exp Toxicol Pathol. 2013 Jul;65(5):541-7. doi: 10.1016/j.etp.2012.03.003. Epub 2012 May 1.
The clinical application of gentamicin has been limited by its nephrotoxicity, which is characterized by kidney injury, interstitial fibrosis and progressive renal impairment. In this paper, we examine effects of plasmid pUDK-HGF which encodes the human hepatocyte growth factor (HGF) gene on gentamicin-induced renal injury in rats. The kidney injury was intentionally induced by injecting gentamicin intraperitoneally. On the third day after last gentamicin treatment, pUDK-HGF was injected into the left kidney tissue only once via a sterile back incision. At day 30 after gentamicin treatment, RI, Scr, BUN, 24 h-UTP and apoptotic cell death were determined. Tubulointerstitial injury and the renal interstitial vessel regeneration were evaluated by histological scoring. pUDK-HGF treatment significantly improved the renal function with decreasing RI, Scr and BUN. 24 h-UTP also presented ameliorating trend compared to the control group with kidney injury. pUDK-HGF treatment significantly decreased the score of tubulointerstitial injury and enhanced angiogenesis, also prevented kidney cells from apoptosis. The tubulointerstitial injury was significantly reduced in the pUDK-HGF injected left kidney and right kidney also showed some improvements. Our results showed that pUDK-HGF may become a novel therapeutic agent for kidney injury and renal fibrosis.
庆大霉素的临床应用因其肾毒性而受到限制，其特征为肾损伤、间质纤维化和进行性肾功能损害。在本文中，我们研究了编码人肝细胞生长因子（HGF）基因的质粒pUDK-HGF对庆大霉素诱导的大鼠肾损伤的影响。通过腹腔注射庆大霉素有意诱导肾损伤。在最后一次庆大霉素治疗后的第三天，仅通过无菌背部切口将pUDK-HGF注射到左肾组织中一次。在庆大霉素治疗后第30天，测定肾阻力指数（RI）、血清肌酐（Scr）、血尿素氮（BUN）、24小时尿总蛋白（24 h-UTP）和凋亡细胞死亡情况。通过组织学评分评估肾小管间质损伤和肾间质血管再生情况。pUDK-HGF治疗显著改善了肾功能，RI、Scr和BUN降低。与肾损伤对照组相比，24 h-UTP也呈现出改善趋势。pUDK-HGF治疗显著降低了肾小管间质损伤评分，增强了血管生成，还防止了肾细胞凋亡。注射pUDK-HGF的左肾肾小管间质损伤明显减轻，右肾也有一些改善。我们的结果表明，pUDK-HGF可能成为治疗肾损伤和肾纤维化的新型治疗药物。
