腺病毒Smad7转染对阿霉素肾病大鼠蛋白尿的影响  

Effect of adenovirus-mediated Smad7 gene transfer on proteinuria of Adriamycin-induced nephropathy rat model

作　　者：冯笑琪 林娜娜[1] 谢燕媚[1] 纪泽泉[1] 

机构地区：[1]广州医科大学附属第二医院,广东广州510260

出　　处：《中国现代医学杂志》2016年第6期1-5,共5页China Journal of Modern Medicine

摘　　要：目的在阿霉素(ADR)肾病大鼠模型中,探讨过表达Smad 7对肾病蛋白尿及其病理的影响。方法本实验用单次尾静脉注射建立阿霉素肾病模型,通过构建重组腺病毒介导外源性Smad 7基因,单侧肾动脉灌注转染Smad 7至靶肾脏。用荧光显微镜检测Smad 7重组腺病毒的转染效果,用邻苯三酚红比色法测定大鼠24 h尿蛋白,HE染色检测各组肾脏病理改变。结果 1用6.5 mg/kg ADR一次性尾静脉注射SD大鼠可成功构建肾病模型;4周末似微小病变型肾病。2单侧肾动脉灌注能有效将介导Smad 7的重组腺病毒转染至大鼠靶肾脏。34周末肾病重组腺病毒(Ad-Smad7)组尿蛋白(38.4±6.0)较ADR组(69.58±10.63)减少(P<0.05)。4荧光显微镜显示肾病Ad-smad7组大鼠靶肾中,Ad-Smad7主要在肾小管表达,肾小球表达少。5肾病Ad-Smad7组肾脏病理改变轻微,肾病Ad-GFP组、ADR组病理较严重,出现类似局灶节段性肾小球硬化的慢性肾脏病病理表现。结论单侧肾动脉灌注有效地使重组腺病毒介导的Smad 7转染至大鼠靶肾脏,使Smad 7在该肾过表达,可减轻肾病大鼠蛋白尿,并改善阿霉素肾病病理。Ojective To investigate the effect of overexpression of Smad7 on proteinuria and renal pathology in the Adriamycin-induced nephropathy（ADN） rat model. Methods ADN model was established by single tail intravenous injection of Adriamycin（ADR）. Smad7 gene was transferred by means of infusing a recombinant adenovirus into the left renal artery. Recombinant adenovirus-Smad7（Ad-Smad7） was detected under fluorescence microscope. HE staining was used to examine renal pathological changes of each group. Pyrogallol red colorimetry was used to detect24-h urinary protein. Results SD rats received a single intravenous injection of ADR（6.5 mg/kg）, which constructed the ADN model. The pathology was similar to minimal change nephropathy at the fourth weekend. Unilateral renal artery infusion was efficient to transfer Ad-Smad7 to the target kidney. Urinary protein of the Ad-Smad7 group（38.4 ±6.0） decreased compared to the ADR group（69.58 ± 10.63） at the fourth weekend（P〈0.05）. Smad7 was mainly expressed in renal tubular epithelia in the Ad-Smad7 group, scarcely seen in glomeruli. The pathological changes of the Ad-Smad7 group were mild, while the changes of the Ad-GFP and ADR groups were similar to focal segmental glomerulosclerosis. Conclusions Ad-Smad7 can be transferred to the target kidney through unilateral renal artery infusion, and overexpression of Smad7 can ameliorate proteinuria and pathological changes of Adriamycin-induced nephropathy.

关 键 词：重组腺病毒 SMAD 7 肾病 蛋白尿 

分 类 号：R725.7[医药卫生—儿科]