APP17肽对糖尿病KK小鼠肾脏的保护作用

Effect of APP17 peptide on the nephropathy in type 2 diabetic KkAy mice

目的 观察 App17肽对 2型糖尿病小鼠尿白蛋白、总蛋白排泄量和肾脏超微结构的影响。 方法 KKAy小鼠 ,根据血糖水平分为 :血糖正常组 (C组 ) ,糖尿病组 (D组 )和 17肽治疗组 (D+17P组 ) ,17肽治疗组给予 APP17肽皮下注射。 12周后将 3组小鼠处死。处死前 1d,用代谢笼收集小鼠 2 4 h尿量 ,测总蛋白、白蛋白值 ;处死时心脏取血测血糖及血胰岛素水平 ;取肾皮质送电镜检查。 结果 (1) D组小鼠肾小球基底膜明显增厚 ,近曲小管出现大量空泡和退变钙化的线粒体 ,而 C组和 D+17P组小鼠无此改变。 (2 )三组小鼠尿总蛋白和尿白蛋白排泄量由低到高依次为 C≤ D+17P≤ D(P<0 .0 5 )。 (3) D组和 D+17P组小鼠的血糖、糖化血红蛋白、胰岛素水平比 C组明显升高 (P<0 .0 5 ) ,D组和 D+17P组之间差异无显著性 (P>0 .0 5 )。 结论 App17肽对 KKAy糖尿病小鼠肾脏病变具有保护作用 。

Objective (1)To observe the effect of APP17 peptide on diabetic renal ultrastructure. (2) To study the excretions of urinary albumin and total protein in genetically obese and diabetic yellow KK(KK Ay) mice. Methods 1. The KK mice were divided into three groups according to the level of blood sugar: group of normal control (C), group of DM (D) and group treated with APP17 peptide (D+17P) subcutaneously in the dose of 8mg/kg, three times a week, for 12 weeks. The following indexes were investigated: (1) The 24 hour urine of each mouse were obtained to evaluate the amount of total protein and albumin. (2) The blood samples were obtained to evaluate the blood sugar and plasma insulin. (3) After fixation by transcardiac perfusion, 5 mice were selected randomly from each group and their renal cortexes were observed by using electron microscope. Results (1)Ultrastructure of kidney of mice in DM group showed more vacuole and degenerated and calcified mitochondria in areas of proximal convoluted renal tubules. The basal membrane became thicker markedly, while there was no the above changes in kidney of C group and D+17P group. (2)The blood sugar, hemoglobin and insulin of mice in D group and D+17P group were much higher than those of C group ( P <0.05).(3) But these indexes showed no significant difference between D group and D+17P group ( P >0.05), which indicated that APP17 peptide had no influence on the glucose metabolism. Conclusion APP17 peptide may play a protective role in diabetic nephropathy.