【作者】 陈娣；

【导师】 吕永曼；

【作者基本信息】 华中科技大学 ， 肾脏内科， 2007， 硕士

【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周分别处死5只糖尿病大鼠和正常组大鼠,检测各组大鼠的血糖、血尿素氮、血清肌酐、24小时尿量及尿肌酐,以免疫比浊法检测大鼠24小时尿微量白蛋白水平和尿白蛋白/尿肌酐比值,同时以肾小球足细胞表面标志物肾母细胞瘤抑制基因(Wilm’s tumor1,WT1)水平检测足细胞密度变化,及RT-PCR法测定各组大鼠肾皮质α3β1整合素mRNA的表达水平。结果与正常组相比,糖尿病大鼠从2周起就出现了明显的足细胞密度减低(p<0.01),24小时尿量、尿微量白蛋白和尿白蛋白/尿肌酐增加(p<0.01),4周开始出现血尿素氮升高(p<0.01),8周开始出现血清肌酐升高(p<0.01),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周起较正常组有明显降低(p<0.01),β1整合素mRNA水平在12周降至最低。而α3整合素mRNA在4周,6周,8周,12周并没有呈现持续的减少。α3整合素mRNA与肾小球WT1面密度呈显著正相关(r=0.782, p<0.01),与24h尿白蛋白/尿肌酐呈显著负相关(r=-0.632,p<0.01);β1整合素mRNA与肾小球WT1面密度呈显著正相关(r=0.574, p<0.01),与24h尿白蛋白/尿肌酐呈显著负相关(r=-0.724,p<0.01)。结论在糖尿病肾病病程进展中,α3β1整合素水平降低可能是导致足细胞密度减少的主要原因之一,从而导致了糖尿病肾病蛋白尿发生和肾小球损伤的进展。更多还原

【Abstract】 Objective To investigate the changes ofα3β1 integrin mRNA levels, and the correlation with podocyte loss,microalbuminuria in diabetic rats.Methods An animal model of diabetic nephropathy was induced by intraperitoneal injection of streptozotocin.The rats were sacrificed at week 2,4,6,8,12 after model established.Blood glucose,urea nitrogen,creatinine of blood and urine,urine volume of 24 hours were tested.Wilm’s tumor1,microalbumin of urine,renal cortex expression ofα3β1 integrins were examined.Results Compared with the control group, from the second week the podocytes significantly decreased, the urine volume of 24 hours and the microalbuminuria significantly increased, so did the blood urea nitrogen in the fourth week and the blood creatinine in the eighth week.The mRNA levels ofα3β1 integrin obviously decreased from the second week,the mRNA level ofβ1 integrin was the lowest in the twelth week,but the mRNA level ofα3 integrin later didn’t decrease any more. The mRNA expression ofα3 integrin correlated positively with the intensity of wilm’s tumor1(r=0.782,p<0.01),however,correlated negatively with the amount of urinary albumin per creatinine(r=-0.632,p<0.01); the mRNA expression ofβ1 integrin correlated positively with the intensity of wilm’s tumor1(r= 0.574,p<0.01),however, correlated negatively with the amount of urinary albumin per creatinine(r=--0.724,p<0.01).Conclusion The downregulation ofα3β1 integrins in DN may lead to podocyte loss and proteinuria.更多还原