槲皮素降低肾小球周期素激酶抑制剂p27水平改善糖尿病肾病

Quercetin protected the diabetic glomerulus through decreasing the level of the cyclin-kinase inhibitor p27

目的 探讨槲皮素改善糖尿病肾病与肾小球周期素激酶抑制剂 p2 7的关系。 方法 腹腔注射链脲佐菌素建立糖尿病 (DM )模型 ,分为DM +Qu组 ( 6只 )及DM组 ( 6只 ) ,分别给予槲皮素 10 0mg·kg-1·d-1及同体积的生理盐水灌胃 8周 ;对照组 (正常大鼠 6只 )予等体积生理盐水灌胃 8周。采用蛋白印迹 (Western杂交 )方法测定肾小球裂解液 p2 7蛋白水平 ,采用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 DM组大鼠肾小球 p2 7水平为 18.5± 4.3 ,尿白蛋白排泄为 ( 3 9.62± 3 .68) μg/ 2 4h ,肾重 /体重比例为 ( 14.87± 2 .0 2 )× 10 -3,均较其他 2组明显增加 ,ECM蛋白水平也较其他 2组明显增加。与DM组相比 ,DM +Qu组肾小球 p2 7水平 ( 10 .6± 3 .1)、ECM蛋白水平、尿白蛋白排泄 [( 17.62± 3 .0 2 ) μg/ 2 4h]及大鼠肾重 /体重比例 [( 11.3 5± 1.76)× 10 -3]均明显降低 (P <0 .0 1) ;DM +Qu组的血糖水平无明显改变。结论 槲皮素可能通过降低肾小球 p2

Objective To investigate the relationship between the cyclin-kinase inhibitor p27 and the protecting effect of Quercetin on the diabetic glomerulus. Methods STZ-induced diabetic rats were given Quercetin 100 mg·kg -1·d -1 for 8 weeks. The p27 protein of glomerular lysate was detected with Western blotting analysis. The extracellular matrix (ECM) protein (type Ⅳ collagen and fibronectin) of glomerular lysate and 24 h urine albumin were examined with ELISA. Results Glomerular p27 protein and ECM were increased in diabetic rats. Meanwhile, the 24 h urine albumin excretion was elevated proportional to the ratio of kidney weight over body weight in diabetic rats. Quercetin decreased glomerular p27 level (10.6±3.1 vs 18.5±4.3, P<0.01), 24 h urine albumin excretion [(17.62±3.02) μg/24 h vs (39.62±3.68) μg/24 h, P<0.01], and the ratio of kidney weight over body weight [(11.35±1.76)×10 -3 vs (14.87±2.02)×10 -3, P<0.01] of diabetic rats. The blood glucose remained constant in diabetic rats and Quercetin-treated diabetic rats.Conclusion Quercetin protected diabetic glomerulus through decreasing glomerular p27 level.