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作 者:陈娣[1] 肖婧[1] 张林娟 吕永曼[1] 邵菊芳[1]
机构地区:[1]华中科技大学同济医学院附属同济医院肾内科,武汉市430030
出 处:《医学分子生物学杂志》2007年第4期293-298,共6页Journal of Medical Molecular Biology
摘 要:目的动态观察1型糖尿病大鼠肾小球足细胞及粘附分子α3β1整合素表达的时相变化,探讨α3β1整合素与足细胞减少,蛋白尿发生的关系。方法以1型糖尿病大鼠为动物模型,于第2,4,6,8,12周以肾小球足细胞表面标志物肾母细胞瘤抑制基因(Wilm’stumor1,WT1)水平检测足细胞密度变化,同时以免疫比浊法检测大鼠24h尿微量白蛋白水平,及RT-PCR法测定各组大鼠肾皮质α3β1整合素mRNA的表达水平。结果与对照组相比,糖尿病大鼠从2周起出现明显的足细胞密度减低,24h尿量和尿微量白蛋白增加,4周开始出现血尿素氮升高,8周开始出现血清肌酐升高,并且随着病程进展,足细胞密度和24h尿微量白蛋白水平变化更加明显。α3β1整合素mRNA水平从第2周起比正常对照组明显降低,而在4周、8周和12周并没有呈现持续的减少。结论在糖尿病肾病早期,α3β1整合素水平降低可能是导致足细胞减少和蛋白尿发生的主要原因,而随着糖尿病病程进展,可能有其他机制参与,从而导致了糖尿病肾病足细胞减少、蛋白尿发生和肾小球损伤的进展。Objective To investigate the changes of α3β1 integrin mRNA levels and the correlation between podocyte loss and proteinuria in diabetic rats. Methods An animal model of diabetic nephropathy was induced by intraperitoneal injection of streptozotocin. The rats with diabetic nephropathy were sacrificed 2, 4, 6, 8, 12 weeks after model establishment. Wilm' s tumor, urinary microalbumin, the expression of α3β1 integrins in renal cortex were examined. Results Compared with the control group, from the 2nd week, the podocytes significantly decreased, the 24-hour urine volume and the microalbumin increased significantly and so did the blood urea nitrogen in the 4th week and the blood creatine in the 8th week. The mRNA levels of α3β1 integrins obviously decreased from the 2nd week, but thereafter it ceased to drop. Conclusion The downregulation of α3β1 integrins in the early DN may lead to podocyte loss and proteinuria and in the late stage other factors may be involved in the progression of DN.
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