1,25-(OH)2D3对阿霉素肾病鼠肾小球肌营养不良蛋白聚糖表达的影响

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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 expression of dystroglycan (DG) and the effect of 1,25 (OH) 2D3 on the expression of glomerular dystroglycan in adriamycin-induced nephropathy rats. Methods: Male Wistar rats were randomly divided into control group and model group with ADR nephropathy. The latter model was induced by ADR induced by caudal vein and then divided into ADR group and ADR + 1,25- (OH) 2D3 group. ADR + 1,25- (OH) 2D3 groups were implanted subcutaneously with osmotic micropumps, giving 1,25- (OH) 2D3450ng / (kg.min) for 6 weeks. Urine red blood cells, urinary protein, urinary podocytes (UPC) and serum albumin (SA), total cholesterol (TC) and triglyceride (TG) were detected. Kidney electron microscopy podocytes (PC) number, the average width of the foot process. Glomerular fluorescence staining quantitative detection of glomerular α (β) -DG protein expression. Results: Compared with the control group, urinary erythrocytes, urinary protein, UPC, TC, TG and AD of rats in ADR group were significantly higher than those in control group (P <0.05) Fluorescent staining was segmental loss, fluorescence intensity decreased significantly. Compared with the ADR group, urinary erythrocytes, urinary protein, UPC, TC and TG decreased obviously in ADR + 1,25- (OH) 2D3 group and SA increased significantly; PC number increased significantly and the width of foot process decreased significantly; α (β) -DG fluorescence staining linear fluorescence, fluorescence intensity increased significantly. There was a significant positive correlation between UPC and urinary protein. The light intensity of α-DG and β-DG was negatively correlated with the width of foot process and positively correlated with PC number. Conclusion: The expression of α (β) -DG in ADR nephropathy rats decreased. 1,25- (OH) 2D3 can reduce excretion of urinary protein and UPC, increase the expression of α (β) -DG, decrease PC shedding and maintain the number of glomerular PC in ADR nephropathy rats.
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