后肾间充质细胞移植治疗大鼠慢性阿霉素肾病

Treatment of metanephric mesenchymal cells transplantation for adriamycin-induced chronic nephropathy rats

目的探讨大鼠胚胎后肾间充质细胞（MMC）尾静脉移植对慢性阿霉素（ADR）肾病大鼠的治疗作用：方法90只雌性SD大鼠被随机分为阿霉素肾病组（n=40，间隔3周2次尾静脉注射阿霉素0.25mg／100g）、MMC移植组（n=40，于第2次阿霉素注射后8周，尾静脉注射5×10^6—7×10^6MMC）、对照组（n=10）。于细胞移植后第8周杀鼠，留取肾组织行病理学分析；免疫组织化学检测肾组织Ⅳ型胶原、基质金属蛋白酶2（MMP-2）、基质金属蛋白酶9（MMP-9）的表达；Western印迹及RT-PCR分别对MMP-2、MMP-9的蛋白及基因表达进行半定量检测：结果MMC移植组和阿霉素肾病组肾小管损伤指数及肾小球硬化面积差异无统计学意义（P〉0.05）。与阿霉素。肾病组比较，细胞移植组肾组织Ⅳ型胶原沉积减少，MMP-2蛋白及基因表达下调，MMP-9蛋白及基因表达升高，差异均有统计学意义（均P〈0.05）。结论MMC移植对阿霉素大鼠肾组织纤维化有潜在的治疗作用，MMP降解途径的激活可能在其中发挥了作用。

Objective To detect the functional repair of metanephric mesenchymal cells （MMCs） transplantation in adriamyein （ADR）-induced glomerulopathy rats. Methods A total of 90 Sprague-Dawley female rats were randomly divided into three groups： ADR group （n=40, rats were injected via the tail vein with 0.25 mg ADR/100g body weight on days 1 and 21）, ADR-MMCs group （n=40, rats were injected via the tail vein with 5×10^6-7×10^6 MMCs 8 weeks after the seeoml ADR administration）, control （n=10）. All the rats were scarified 8 weeks after MMCs injection. Pathology and collagen 1V expression in renal tissue were examined. Moreover, matrix metalloproteinases 2 （MMP-2） and matrix metalloproteinases 9 （MMP-9） expression in the renal tissue were also detected with immunohistochemistry, and quantity analysis of protein and gene was further demonstrated with Western blot and RT-PCR analysis, respectively. Results There were no signifieant differences in tubulointerstitial injury score and glomerulosclerosis degree between ADR group and ADR-MMCs group （P〉0.05）. Compared with ADR group, collagen Ⅳ and MMP-2 expression decreased, MMP-9 expressioll increased in renal tissue of ADR-MMCs group, and the difference was significant （P〈0.05）. Conclusion MMCs transplantation may have potentially Iherapeutic effect on renal tissue fibrosis of adriamyein-indueed glomerulopathy in rats,and the signaling pathways of MMPs appear to be involved in these processes.