hHGF基因肾脏电转染对大鼠慢性移植肾病的影响  

Efficacy of direct kidney electrotransfer of hHGF gene in preventing CAN in rats

作　　者：李宓[1] 杜艺[1] 陈家湄[1] 彭莉[1] 邹和群[1] 

机构地区：[1]中山大学附属第五医院肾内科,珠海519000

出　　处：《中国免疫学杂志》2007年第6期510-512,517,共4页Chinese Journal of Immunology

基　　金：广东省自然科学基金项目资助(编号:04009419)

摘　　要：目的:使用肾脏直接基因电转染方法对大鼠移植肾进行hHGF基因转染,观察该基因对防治大鼠慢性移植肾病的作用。方法:雄性SD大鼠20只,随机分为治疗组和对照组,每组10只。利用移植肾离体灌流时机将含有hHGF基因的质粒(治疗组)及空质粒(对照组)用电转染方法转入大鼠肾脏,并行自体肾移植及对侧单肾切除。于移植第8天及12周后观察hHGF基因在肾组织中的表达,并对移植肾进行功能和组织学评价。结果:治疗组肾组织hHGF基因表达于移植后第8天为阳性,对照组及治疗组移植后12周hHGF基因表达阴性,治疗组血浆hHGF水平在电转染后第7天为(76.9±11.7)pg/ml,第12周的hHGF浓度为0,而对照组第7天及第12周均未测到hHGF。治疗组血肌酐、尿素氮水平于移植后12周显著低于对照组。组织学评价显示,于肾移植后12周,治疗组肾间质纤维化程度显著轻于对照组。结论:hHGF基因转染治疗对减轻移植肾的肾功能损伤和肾间质的纤维化具有远期效果,这种远期效果可能与hHGF基因对移植肾早期缺血再灌注损伤的保护作用及抗纤维化作用有关。因此,本组认为hHGF基因转染在肾移植初期的治疗作用对预防慢性移植肾病的发生和发展起了重要的作用。Objective：To investigate the efficacy of direct electrotransfer of hHGF gene in preventing chronic allograft nephropathy（CAN） , hHGF gene was transferred into rat kidney with electrotransfer assay. Methods ：20 male SD rats were divided randomly into study group and control group, 10 in each group. The plasmid of hHGF gene（ study group） and empty plasmid（ control group） was transferred into the transplanted rat kidney. Next, the rat kidney was autotransplanted and the eontralateral kidney was removed. The pharmaeokinetic of hHGF and the function and histological change of the kidney at 8 days and 12 weeks after transplantation were determined. Results：The expressions of hHGF in the renal tissue and plasma was positive at 8 days after transplantation of the animals in study group and negative at 12 weeks after transplantation in study group or in control in same time. The serum creatinine and Bun levels in controls group were significantly higher than in study group at 12 weeks after transplantation and before transplantation. It was shown by histological evaluation that there were less interstitial fibrosis in study group compared to controls at 12 weeks after transplantation. Conclusion：It is indicated that the direct kidney electrotransfer of hHGF gene was effective in preventing renal function injury and interstitial fibrosis of the transplanted kidney. It is relation of transfection of hHGF gene into the rat renal with reimplantation of the kidney suppressed tubulointerstitial injury and subsequent fibrosis in context of induced inehemia. The results suggest that the initial prevalence of hHGF may he sufficient to prevent chroncic allograft nephropathy.

关 键 词：慢性移植肾病 人肝细胞生长因子 基因治疗 

分 类 号：R392.4[医药卫生—免疫学]