携带人肝细胞生长因子重组质粒pUDK-HGF对大鼠肾纤维化的防治作用

Recombinant Plasmid pUDK-HGF Encoding Human Hepatocyte Growth Factor Gene Retards Renal Fibrosis in Rats

目的:研究肝细胞生长因子(HGF)基因转导对庆大霉素诱导的大鼠肾纤维化损伤的防治效果。方法:以雄性Wistar大鼠腹腔注射硫酸庆大霉素注射液制备肾纤维化模型;实验分为正常对照组、肾纤维化模型组、HGF治疗组;造模后第30 d,HGF治疗组于左侧肾脏直接注射重组质粒pUDK-HGF注射液,模型组注射质粒pUDK,正常对照组只进行假手术;于造模后第60 d处死大鼠,评价HGF对血尿素氮、血肌酐、24 h尿蛋白、肾系数等肾功能指标的改善作用,并对肾纤维化进行组织学评价。结果:与正常对照组相比,模型组肾功能下降,肾系数(8.8±0.95 g/kg)、血尿素氮(9.4±2.61 mmol/L)、血肌酐(42±10.33μmol/L,P<0.05)及24 h尿蛋白定量(25.78±8.66 mg,P<0.05)升高;HGF治疗组对肾功能有所改善,可缓解肾纤维化的进展。此外,本实验表明,对已纤维化肾脏直接注射HGF基因,可促进肾间质血管再生,并进一步降低肾小管间质损伤积分。结论:将HGF基因靶向导入大鼠体内可有效防治肾纤维化。

Objective： To investigate the effects of hepatocyte growth factor（HGF） gene on gentamicininduced re nal fibrosis in rats. Methods： Male Wistar rats were injected gentamicin sulphate intraperitoneally to cause renal fibrosis. All rats were divided into control group, model group, HGF treatment group. On the 30th day after model ing, HGF treatment group animals were transferred pUDKHGF into the left kidney, while those of model group were administered pUDK as an empty plasmid control. The rest were carried out shamoperation. All rats were ex ecuted on the 60th day after modeling. The urine volume and blood samples were used for the determination of se rum creatinine（Scr）, blood urea nitrogen（BUN） and 24hurine total protein（24hUTP）. The kidneys were excised for histological evaluation and assessment of renal index（RI）. Results： Gentamicin caused a reduction in renal function with increasing in RI （8.8＋0.95 g/kg）, BUN （9.4_＋2.61 mmol/L）, Scr（42_＋ 10.33 Ixmol/L, P〈0.05） and 24hUTP （ 25.78 _＋ 8.66 mg, P〈0.05） compared with control group. HGF treatment could improve renal function, then alleviate renal fibrosis. In addition, this study confirmed that HGF could promote angiogenesis and further re duce tubulointerstitial injury. Conclusion： Targeted transfer of HGF gene will ameliorate renal interstitial fibrosis in rats effectively.