1,25-(OH)_2D_3对阿霉素肾病鼠肾小球肌营养不良蛋白聚糖表达的影响

1,25-Dihydroxyvitamin D3 increase the expression of dystroglycan in rats with adriamycin nephropathy

目的:观察阿霉素(ADR)肾病鼠肾小球肌营养不良蛋白聚糖(dystroglycan,DG)的表达及1,25-(OH)2D3对其表达的影响。方法:雄性Wistar大鼠随机分为对照组和ADR肾病模型组;后者经尾静脉注射ADR诱导肾病模型,再随机分ADR组、ADR+1,25-(OH)2D3组。ADR+1,25-(OH)2D3组皮下埋置渗透性微量泵,给予1,25-(OH)2D3450ng/(kg.min),连用6周。检测大鼠尿红细胞、尿蛋白、尿足细胞(UPC)及血清白蛋白(SA)、总胆固醇(TC)、甘油三酯(TG)。肾组织电镜检测足细胞(PC)数、足突平均宽度。肾小球荧光染色定量分析检测肾小球α(β)-DG蛋白的表达。结果:与对照组相比,ADR组大鼠尿红细胞、尿蛋白、UPC、TC、TG明显升高,SA明显降低;PC数显著减少,足突宽度增加;肾小球α(β)-DG荧光染色呈节段性缺失,荧光强度显著减弱。与ADR组相比,ADR+1,25-(OH)2D3组尿红细胞、尿蛋白、UPC、TC、TG明显下降,而SA显著增加;PC数明显增加,足突宽度显著减少;肾小球α(β)-DG荧光染色恢复线型荧光,荧光强度显著增加。UPC与尿蛋白显著正相关;α-DG、β-DG光强度值与足突宽度呈负相关,与PC数呈正相关。结论:α(β)-DG在ADR肾病鼠中的表达减少。1,25-(OH)2D3可减少ADR肾病鼠尿蛋白及UPC的排泄,上调α(β)-DG的表达,减少PC脱落,维持肾小球PC数量。

Objective To observe the effect of 1,25-（OH）2D3 on glomerular dystroglyean （DG） expression in rats with adriamyein（ADR） nephropathy. Methods Wistar rats were randomly divided into two groups： control group, ADR model group which was induced by ADR injected into the tail vein. After these models were successfully established, they were randomly divided into two groups： ADR group, ADR＋1,25-（OH）2D3 group with 1,25-（OH）2D3 therapy. ADR＋ 1,25- （OH） 2D3 group was embedded with the osmotic minipump for giving 450 ng/（kg, min） 1,25- （OH）2D3. After the treatmemt with 1,25-（OH）2D3 for 6 weeks, haematuria, proteinuria, urinary podoctye（UPC）, serum albumin（SA）, total eholesterol（TC）, triglyeride（TG） were measured. Average numbers of podoeytes per field of vision and the mean width of foot proeesses were deteeted under eleetron mieroscopy. The expression of α（β）-DG protein in glomeruli was detected with immunofluoreseenee staining quantitative analysis. Results Compared with control group, the level of urine erythroeyte, urine protein, UPC, TC, TG in ADR group was significantly increased, SA decreased; average numbers of podoeytes per field of vision was dramatically reduced; the mean width of foot processes was inereased; the expression of α（β）-DG was obvious absenee in glomeruli by immunofluoreseene; fluorescence intensity was significantly weakened. Compared with ADR group, the level of urine erythrocyte, urine protein, UPC, TC, TG in ADR＋1, 25-（OH）2D3 group was significantly decreased, SA increased; the numbers of podocytes per field of vision was increased; the mean width of foot processes was reduced; glomerular α（β）-DG staining was restored to a linear-like pattern; fluorescence intensity was statistically increased. There was a significantly positive correlation between UPC and urine protein. Fluorescence intensity of α-DG, β-DG showed a negative correlation with the mean width of foot processes and positive correlation with the number of podocytes. Conclusion The expression of α（β）-DG was reduced in rats with adriamycin nephropatby. 1,25-（OH）2D3 could contribute to decrease the excretion of urine protein and UPC, upregulate the expression of α（β）-DG, decrease podocyte detachmen and maintain podocyte number.