摘要
目的探讨1,25-(OH)2D3对局灶节段性肾小球硬化(FSGS)大鼠尿足细胞(UPC)排泄及肾小球WT-1蛋白分布的影响。方法24只SD大鼠分为3组:对照组、FSGS组、1,25-(OH)2D3组。采用左肾摘除,阿霉素重复注射诱导FSGS大鼠模型。1,25-(OH)2D3组在第1次给予阿霉素后1周埋植渗透性微量泵按0.03ng/(g·d)皮下给予1,25-(OH)2D3。实验10周末检测尿白蛋白排泄率(UAER)、尿转化生长因子-β1(TGF-β1)及结缔组织生长因子(CTGF)。免疫荧光法检测尿沉渣足细胞特异性标志蛋白Wilm'stumor-1(WT-1),观察肾小球WT-1的分布。尿WT-1荧光细胞即为尿液足细胞。结果FSGS组UPC、UAER、TGF-β1、CTGF、肾小球细胞数及细胞外基质(ECM)/肾小球毛细血管襻面积均较对照组明显升高(P<0.01)。与FSGS组相比,1,25-(OH)2D3组UAER、ECM/肾小球毛细血管襻面积显著降低(P<0.01),UPC、TGF-β1、肾小球细胞数亦降低(P<0.05),CTGF无统计学意义(P>0.05)。肾小球荧光染色示WT-1在对照组正常,FSGS组呈节段性缺失,1,25-(OH)2D3组缺失较轻。UPC与UAER呈正相关(rs=0.42,P<0.05),TGF-β1与CTGF亦呈正相关(rs=0.47,P<0.05)。结论尿液中脱落足细胞检测可作为判断FSGS病情活动性的标志之一。1,25-(OH)2D3可减轻FSGS大鼠UPC、UAER、TGF-β1的排泄,抑制肾小球细胞数及ECM增殖,恢复肾组织WT-1表达而有肾保护作用。
Objectives To investigate the effect of 1, 25-（OH） 2D3 on the excretion of urinary podocytes （UPC） and glomerular distribution of Wilm＇s tumor-1 （WT-1） in focal segmental glomerulosclerosis （FSGS） rats. Methods Twenty-four Sprague-Dawley rats were divided into three groups, which are control group; FSGS group; 1,25-（OH）2D3 group. Rats had left nephrectomy and were then injected with adriamycin （ADR） twice to induce FSGS model. 1,25- （OH）2D3 group in which rats were injected with ADR and one week later treated with 1,25-（OH）2D3 at 0.03 ng/（g.d） by subcutaneous implantation of osmotic minipumps until the end of the study. The urinary albumin excretion rate （UAER）, transforming growth factor-β1 （TGF-β1）, and connective tissue growth factor （CTGF） were measured in the weekend of study week 10. Podoeyte specific marker protein WT-1 was detected in urinary sediment. The glomerular distribution of WT-1 was observed by immunofluorescene. Urinary WT-1-positive cells were identified as UPC. Results UPC, UAER, TGF-β1, CTGF, glomerular cell numbers, and the ratio of accumulation of extracellular matrix （ECM） to the area of glomerular capillary were significantly higher in FSGS group than those in control group respectively （P 〈 0.01 ）. Compared with FSGS group, in 1,25-（OH）2D3 group, UAER and the ratio of ECM to area of glomerular capillary were significantly lower （P 〈 0.01） ; UPC, TGF-β1, and. glomerular cell number were also significantly lower （P 〈 0.05） ; CTGF was not statistically different （P 〉 0.05）. The expression of WT-1 in glomeruli measured by immunofluorescene was normal in control group while it was focal absence in FSGS group and slightly absence in 1,25-（OH）2D3 group. UPC was positively correlated with UAER （r, = 0.42, P 〈 0.05） and TGF-β1 positively correlated with CTGF （r, = 0.47, P 〈 0.05）. Conclusions Urinary podocyte could be one of the markers to predict the development of FSGS. 1,25-（OH）2D3 decrea
出处
《临床儿科杂志》
CAS
CSCD
北大核心
2008年第4期291-294,共4页
Journal of Clinical Pediatrics
