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糖尿病大鼠肾小球周期素激酶抑制剂p27的变化及意义 被引量:12

The significance of glomerular cyclin-kinase inhibitor p27 in diabetic rats
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摘要 目的 :探讨糖尿病肾小球周期素激酶抑制剂p2 7水平的变化及p2 7在糖尿病 (DM)肾小球细胞 (特别是系膜细胞MC)肥大中的作用。  方法 :蛋白印迹 (Western杂交 )方法测定肾小球裂解液p2 7蛋白水平 ,RT PCR方法测定肾小球p2 7mRNA ,ELISA方法测定肾小球裂解液细胞外基质 (ECM)蛋白 (Ⅳ型胶原及纤维连接蛋白 )和尿白蛋白。  结果 :随着DM病程的延长 ,DM大鼠肾小球p2 7水平和肾小球ECM蛋白水平逐渐增高 ,2 4h尿白蛋白排泄量逐渐增加 ,同时DM大鼠肾重 /体重呈增高趋势。DM(2 8天 )大鼠与正常大鼠间肾小球p2 7mRNA无差别。不同病程糖尿病大鼠间全血血糖浓度无明显差异。  结论 :DM大鼠肾小球p2 7水平增高 ,p2 7水平增高可能在DM大鼠肾小球细胞肥大 (特别是MC肥大 )中起重要作用。 Objective:To investigate the significance of glomerular cyclin-kinase inhibitor p27 in the different phases of diabetes mellitus(DM)and the potential effect of p27 on the hyperthrophy of diabetic glomerular cells(especially mesangial cell,MC). Methodology:Thirty SD rats,male,weight of 180 to 200 gram,were divided into two group.They were diabetic group,treated with streptozotocin(STZ)65 mg/kg in peritoneal injection and blood glucose more than 13.8 mmol/L after 48 hours,and control group,treated with saline in peritoneal injection.The diabetic rats were sacrificed at the 7,14,21,and 28th day.The p27 protein of glomerular lysate was detected with western blotting analysis.The p27 mRNA was determined with technique of RT-PCR.The extra-cellullar matrix(ECM)protein(type Ⅳ collagen and fibronectin)in glomerular lysate,and the albumin excretion in 24h urine were examined by ELISA. Results:In diabetic rats,the level of glomerular p27 protein was significantly higher than that in controls,and increased along with the duration of diabetes(4.1±1.1 in 7d,6.2±2.2 in 14d,9.0±2.8 in 21d,and 13.5±3.8 in 28d vs 1.0±0.3 in control).The 24h urinary excretion of albumin and glomerular proteins of ECM was also elevated with the duration of diabetes in diabetic rats.Meanwhile,ratio of kidney weight over body weight showed increasing trend in diabetic rats(4.32±0.90×10 -3 in 7d,4.51±0.91×10 -3in 14d,4.76±0.95×10 -3 in 21d,4.87±1.02×10 -3in 28d vs 4.07±0.83×10 -3 in control).No significant difference in level of glomerular p27 mRNA was found between the 28d diabetic rats and controls.The blood glucose of diabetic rats remained constantly high in the different phases of diabetes. Conclusion:The glomerular level of p27 protein significantly increased in diabetic rats.The high level of p27 may contribute to the hyperthrophy of glomerular cells(especially MC)in diabetes.
出处 《肾脏病与透析肾移植杂志》 CAS CSCD 2002年第1期17-20,共4页 Chinese Journal of Nephrology,Dialysis & Transplantation
关键词 细胞周期调节蛋白 周期素激酶抑制剂 糖尿病肾病 cell cycle regulatory protein cyclin-kinase inhibitor diabetic nephropathy
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  • 1Young B A,Kidney Int,1995年,47卷,935页
  • 2Slingerland J M,Mol Cell Biol,1994年,14卷,3683页
  • 3Wolf G,Kidney Int,1992年,42卷,647页
  • 4Ling H,Nephrol Dial Transplant,1995年,10卷,1305页

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