输注重组GDNF过表达的间质干细胞改善肾毒性血清肾炎肾功能

Transplantation of MSC with Overexpressing Recombinant pAdGDNFGFP Improved Renal Function of Nephrotoxic Serum Nephritis Rats

【目的】观察输注GDNF过表达的骨髓间质干细胞对大鼠肾毒性血清肾炎(NSN)的疗效。【方法】构建含绿色荧光蛋白的胶质细胞源性神经营养因子(GDNF)重组腺病毒表达质粒(pAd-GDNF-GFP)并转染骨髓间质干细胞(MSC)。成年雌性SD大鼠肾毒性血清肾炎模型20只,分为3组,实验组8只大鼠经肾动脉输注转染pAd-GDNF-GFP阳性MSC,6只输注pAd-GFP(不含GDNF)阳性MSC和6只输注培养基作为对照。病理切片HE染色观察各组肾脏病理变化情况,测定血清肌酐(Cr)、尿素氮(BUN)并计算肌酐清除率。对数据组间差异进行ANOVA方差分析。【结果】实验组病理HE染色可见肾小球的病变程度减轻,肾小管坏死和扩张减少,炎症细胞的聚集减少,肾脏组织细胞结构修复完整,提示炎症得到改善。同时实验组蛋白尿症状减轻,血清肌酐(Cr)和尿素氮降低,肌酐清除率改善,与对照组差别具有统计学意义(P<0.05)。【结论】输注GDNF过表达的MSC能够改善NSN大鼠肾功能和逆转发病肾脏的病理改变,起到了较好的治疗效果。

【Objective】 The nephrotoxic serum nephritis animal model was constructed to investigate the therapy effect of glial cell linederived neurotrophic factor（GDNF） overexpression of bone marrow mesenchymal stem cell and improving renal function to the nephrotoxic serum nephritis（NSN）,and the clinical efficacy was evaluated.【Methods】 MSC was transfected with adenovirus expression vector containing GDNF,evaluate the transfection efficiency.Then MSC with overexpressing GDNF was injected to rats through the left renal artery,pathological and biochemical changes were detected to see the improvement of renal function.MSC with GDNF overexpression were located and counted in kidney tissue by fluorescence experiments to evaluate its efficacy.【Results】 After infusion,the MSC were located in the renal cortex,serum creatinine,uremic nitrogen and urinary protein of NSN rats infused pAdGDNFGFP statistically decreased compared with control group,renal function was statistically ameliorated,P 0.05;pathology results showed that the GDNF overexpressing group had lower renal damage score than the control group,P 0.05.【Conclusion】GDNF well improved renal function and pathological changes in NSN rats,the protection of GDNF overexpressing mesenchymal stem cells to NSN rat kidney provided a kind of new idea to for various diseases such as NSN.