糖尿病大鼠血红蛋白糖基化终产物与肾脏改变的关系及意义

目的　探讨糖尿病大鼠血红蛋白糖基化终末产物 (Hb AGE)与肾脏改变的关系。方法采用竞争性酶联免疫吸附分析法 (ELISA)检测 44只 12周和 2 8周病程的链脲佐菌素 (STZ) 糖尿病大鼠和 14只正常对照大鼠的Hb AGE含量 ,并测定尿蛋白 /肌酐 (Pr/Cr)比值及病程 2 8周时的肾小球基底膜厚度 (GBMT)。结果　随着病程的延长 ,Hb AGE水平显著增高 (P <0 .0 1) ,与血糖和HbA1c呈显著性正相关 ,但与HbA1c的关系更密切。Hb AGE与肾小球组织AGE(GTE AGE)含量呈显著性正相关 (r=0 .6 86 2 ,P <0 .0 1) ,二者与尿Pr/Cr比值和GBMT具显著相关性 ;胰岛素和氨基胍可降低Hb AGE水平 ,减少尿蛋白 ,阻止基底膜增厚。结论　Hb AGE可作为AGE循环标志物 ,反映慢性高血糖和肾小球AGE含量 ,有助于了解糖尿病时的肾脏改变 ,其水平长期增高可能是糖尿病肾病的一个危险因素。

Relationship and significance between hemoglobin-advanced glycosylation end products and renal alterations in diabetic rats

Objective To Study the relationship between hemoglobin advanced glycosylation end products (Hb AGE) and renal alterations in diabetes. Methods Hb AGE levels in streptozotocin induced diabetic rats with different duration of diabetes (12 week and 28 week) were measured with competitive enzyme linked immunosorbent assay (ELISA), and urine protein/creatinine (Pr/Cr) ratio in all rats and glomerular basement membrance thickness (GBMT)in28 weekdiabeticratswere determined. Results With increasing duration of diabetes, Hb AGE was significantly increased (P<0.01), which was positively correlated with blood glucose concentration and HbA 1c content, but more closely correlated with the latter. Hb AGE significently positively correlated with glomerular tissue extracts AGE (GTE AGE) (r=0.6862, P<0.01), and both of them were significantly related to urine protein/creatinine ratio and GBMT. Insulin and aminoguanidine reduced Hb AGE levels, decreased urine protein and retarded basement membrane thickening. Conclusion Hb AGE serves as a circulating marker for AGE, reflecting chronic hyperglycaemia as well as glomerular AGE content, which may be useful in understanding of diabetic nephropathy. Long term eleoation of Hb AGE seems a risk factor of diabetic nephropathy.