| Objective:To investigate the relationship between clinical and pathological aspect of early diabetic nephropathy,to search for a early index of diabetic nephropathy,and to explore the possible mechanism of adiponectin in early diabetc nephropathy.Methods:Male wistar rats were randomly assigned into two groups:normal control group(NC)and model group.Normal control group rats were fed with the normal diet,while test group were fed with fat-enriched and highly-energy diet.Hyperglycemia was developed by intraperitoneal injection STZ(30mg/kg)in model group rats after 4 week on this diets.The level of blood glucose were determined 48 hours after the injection and the rats with the blood glucose above 16.7mmol/L were diabetic rats.At 8 weeks proteinuria above 30mg/24h were diabetic nephropathy rats.Then model group rats were randomly divide into three groups:diabetic nephropathy control group(DN),diabetic nephropathy group treated with pIRES2-EGFP(DP)(200μg,biw)and diabetic nephropathy group treated with pIRES2-EGFP-gAd(DA)(200μg,biw). Proteinura and urinary laminin were measured respectively at week 5, week 6,week 7,week 8 and week 10.All rats were sacrificed after week 10.Urea nitrogen(BUN),creatinine(SCR),blood glucose,the scavenging ability of hydroxyl free radicals and MDA of the kidney were measured and analysed.The renal pathologic changes were observed by light microcopy.The expression of TGF-β1 and laminin were examined by immunohistochemistry.Result:1.Body weight was markedly increased in model group as compared with group NC(P＜0.01).Kidney weight/body weight was decreased in model group as compared with group NC(P＜0.01).There were no significant differences in body weight and kidney weight/body weight among the three model groups(P＞0.05).2.Proteinuria and urinary laminin were increased in model group as compared with group NC(P＜0.01).Urinary laminin appeared relatively earlier than proteinuria.3.Blood glucose level was increased in model group as compared with group NC(P＜0.01).BUN and SCR were increased in model group as compared with group NC although this change had no statistical significance(P＞0.05).Blood glucose was decreased in group DA as compared with group DN,DP(P＜0.05).4.The scavenging ability of hydroxyl free radicals was decreased (P＜0.01)and MDA was increased(P＜0.05)in model group as compared with group NC.The scavenging ability of hydroxyl free radicals was increased(P＜0.05)and MDA was decreased in group DA as compared with group DN,DP(P＜0.05). 5.Compared with group NC,there were glomerular hypetrophy, mesangial expansion,tubular epithelial cells cavitation and exfoliation, and mononuclear lymphocyte infiltration in model group.Glomerular sectional area,mesentery area and mesentery area/glomerular sectional area were increased in model group as compared with group NC(P＜0.05). There were no significant differences in Glomerular sectional area, mesentery area and mesentery area/glomerular sectional area among the three model groups(P＞0.05).6.The expression of TGF-β1 and LN in renal tissues were increased in model group as compared with group NC(P＜0.05),especially in renal tubule.The expression of TGF-β1 and LN were decreased in group DA as compared with group DN,NP although this change had no statistical significance(P＞0.05).Correlation analysis showed that urinary LN had positive correlation with expression of LN in renal(r=0.739,p＜0.01);the expression of TGF-β1 had positive correlation with LN in renal tissues(r=0.687,p＜0.01).Conclusion:1.Urinary laminin appears earlier than proteinuria in DN rats.Urinary laminin can be used as an indicator in predicting diabetic nephropathy.2.The expression of TGF-β1 and LN in the kidney of diabetic nepthropathy rats was increased especially in renal tubule.LN deposition may be related to expression of TGF-β1.For LN apperas obviously in renal tubule in early DN,DN renal damage may start from tubule.The scavenging ability of hydroxyl free radicals was decreased and MDA was increased in DN.Oxidative stress is increased in DN.3.Administration of adiponectin to DN rats can reduce hydroxyl free radicals and MDA in the kidney.Adiponectin can inhibit oxidative stress in the kidney,it may help prevent the progression of diabetic nephropathy. |
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