格列喹酮对GK大鼠糖尿病肾病的保护作用

Protective effect of gliquidone on diabetic nephropathy of GK rats

目的:评价格列喹酮对GK大鼠糖尿病肾病的疗效并探讨其相关机制。方法:自发性糖尿病GK大鼠发生糖尿病肾病后,随机分为2组:对照组和格列喹酮组,每组6只,经腹腔埋入微渗泵用药。以6只同龄正常Wistar大鼠为正常组。用药前及用药后每周检测各组大鼠血糖及24h尿白蛋白。用药4周后,留取血清检测C-肽浓度;采集大鼠肾脏组织标本,电镜观察肾小球基底膜及足突的病理改变;采用Real-time PCR检测肾小球晚期糖基化终末产物受体(RAGE)、蛋白激酶C-β(PKC-β)和蛋白激酶A(PKA)的表达。结果:与对照组相比,格列喹酮组大鼠血糖降低、24h尿白蛋白减少、血清C-肽浓度升高。电镜结果显示,格列喹酮组肾小球基底膜厚度减少,足细胞的足突融合缺失、排列不规则明显改善。Real-time PCR结果显示,格列喹酮治疗后肾小球毛细血管RAGE及PKC-β表达降低,PKA表达上调。结论:格列喹酮改善糖尿病肾病GK大鼠的肾小球基底膜及足细胞损伤,减轻蛋白尿,其作用与调节肾小球RAGE、PKC-β和PKA表达,增加C-肽分泌有关。

OBJECTIVE To evaluate the protective effect of gliquidone on diabetic nephropathy of GK rats and explore the relevant mechanism.METHODS 12 spontaneous diabetic GK rats with diabetic nephropathy were randomly divided into 2 groups as following： control group and gliquidone group,6 in each group and all the rats were treated with intraperitoneal micro-osmotic pump.The age-matched 6 normal Wistar rats were used as normal group.Blood glucose and 24 h urinary albumin were measured before treatment and every week during treatment period.After 4 weeks of treatment,concentration of serum C-peptide was detected and kidneys were collected which were observed pathology of glomerular basement membrane（GBM） and podocytes with electron microscope.The expression level of receptor of advanced glycation end products（RAGE）,protein kinase C-β（PKC-β） and protein kinase A（PKA） in glomeruli was evaluated by Real-time PCR.RESULTS Compared with control group,blood glucose and 24 h urinary albumin of GK rats in gliquidone group were decreased.Gliquidone treatment increased the concentration of serum C-peptide.Pathological changes showed that gliquidone significantly reduced the thickness of GBM and ameliorated podocytes morphology compared with control group.The results of Real-time PCR demonstrated that gliquidone downregulated the expression of RAGE and PKC-β,and upregulated the expression of PKA in glomeruli.CONCLUSION Gliquidone ameliorated the injury of GBM and podocytes and reduced urinary albumin involving in downregulating the expression of RAGE and PKC-β,upregulating the expression of PKA in glomeruli,and increasing secretion of C-peptide on diabetic nephropathy in GK rats.