蛋白激酶C对早期糖尿病大鼠肾小球高滤过的影响

EFFECT OF PROTEIN KINASE C ON GLOMERULAR HYPERFILTRATION OF DIABETIC RATS AT EARLY STAGE

探讨蛋白激酶C(ProteinKinaseC ,PKC)对早期糖尿病大鼠肾脏高滤过影响。选用雄性SD大鼠 ,随机分为正常对照组 (C组 )及糖尿病组 (DM组 )。DM组模型制备采用链脲佐菌素 ,饲养至 2周时 ,断头处死。检测两组体重、肾重、2 4h尿白蛋白定量 (放免法 )、内生肌酐清除率 (苦味酸法 )、血浆、肾组织匀浆中一氧化氮合成酶 (NOS)、一氧化氮 (NO)、内皮素 (ET)及肾小球PKC。糖尿病大鼠 2周时 ,血糖、内生肌酐清除率、2 4h尿白蛋白量、肾重 /体重均明显高于正常对照组 (P <0 .0 1)。血浆及肾组织匀浆NO、NOS及肾小球细胞膜PKC均明显高于正常对照组 (P <0 .0 1) ,而ET则低于正常对照组 (P <0 .0 1)。两组肾小球细胞浆PKC相差不显著 (P >0 .0 5 )。两组大鼠肾小球细胞膜PKC与内生肌酐清除率呈正直线相关 (P <0 .0 1)。本研究表明肾脏组织PKC对早期糖尿病肾病高滤过起着重要作用 ,并同NOS及NO关系密切。由高血糖引起的PKC活性升高可能是引起早期糖尿病肾病肾脏肥大、高滤过的主要原因之一。

To investigate the effect of PKC on glomerular hyperfiltration of diabetic rats at early stage. SD rats were divided into control group and streptozotocin induced diabetic group. Rats were killed after two weeks. Body weight, blood glucose, urinary albumin excretion (UAE) , creatinine clearance (Ccr) ,nitric oxide (NO), nitric oxide synthase (NOS) and endothelin(ET) in the plasma and renal cortical tissue were measured. The changes in PKC in the glomeruli were also observed. Blood glucose ,Ccr, UAE, kidney/body weight were significantly elevated in the two week diabetic rats group than control group( P <0.01). Membrane PKC of glomeruli and NO, NOS in the plasma and renal cortical tissue were significantly elevated in diabetic rats than control rats ( P <0.01), but ET were decreased in diabetic group. There were not significant differences in the cytosolic PKC concentration of glomeruli between two groups( P >0.05). Significant positive correlation coefficients were found between membrane PKC and Ccr( P <0.01). This study showed PKC activation in the kidney had very important effect on the hyperfiltration of diabetic nephropathy at early stage,with close relation with NO and NOS. Hyperglycemia induced PKC activation may be the main reason of hyperfiltration and enlargement of kidney at the early stage of diabetic nephropathy.