Potential Relationships Between Renal Changes And Levels Of Insulin-like Growth Factor-1 In Serum And Kidney In Streptozotocin-Diabetic Rats

Objectives: 1. To observe the dynamic changes of insulin-like growth factor-1 (IGF-1) in serum and kidney of the streptozotocin-diabetic rats and the role of IGF-1 in diabetic nephropathy (DN). 2. To observe the therapeutic effect of insulin on the changes of IGF-1 and the pathologic changes of kidney.Methods: 70 male Sprague-Dawlry rats were randomly divided into control group (n=18) and model group (n=52). Model group was induced to hyperglycemia by injecting streptozotocin (STZ) at the dosage of 60mg/kg. Diabetic rat was confirmed by fasting blood glucose(FBG)≥16.7mmol/L after 72 hours of STZ administration (4 cases failed to achieve the standard of diabetes was excluded) and were randomly divided into two groups: diabetes mellitus group (n=24) and insulin treatment group (n=24). Each group was divided into 4,8,12-week groups. Insulin treatment group were injected subcutaneously with long-acting insulin 3u/(100g·d) to control blood glucose. At the same time control group and diabetes mellitus group were injected with 0.2ml 0.9% saline. At the end of the 4th, 8th and 12th week, we collected 24h urine to examine 24h urinary albumin. Blood glucose and body weight were tested. Then rats were killed to collect serum and kidney. we weighed kidney, calculated the ratio of kidney weight to body weight (KW/BW). The levels of IGF-1 in serum were determined by radioimmunity assay (RIA). The morphological changes of kidney were observed through light microscopy after hematoxylin-eosin (HE) staining. Immunohistochemistry staining was used to examine the expression of IGF-1 protein in the kidney.Results: 1. Compared with insulin treatment group and control group, FBG, KW/BW, and 24h urinary albumin were obviously increased in diabetes mellitus group (p<0.01). 2. At the end of the 4th, 8th and 12th week after diabetes mellitus model established, the levels of IGF-1 in serum decreased remarkably in diabetes mellitus group (p<0.01). 3. At the 4th week and 8th week, the expressions of IGF-1 in kidney of diabetes mellitus group were increased significantly (p<0.01). But, at the 8th week the expression of IGF-1 in kidney began to decrease and reached to normal at the end of the 12th week.Conclusions: 1. The decrease of IGF-1 in blood serum and the increase of in kidney are relevant to renal pathological changes of streptozotocin-diabetic rats. 2. The treatment of insulin improved the abnormal changes of IGF-1 in serum and kidney, as well as improved the early pathological changes of kidney in the streptozotocin-diabetic rats.