A Preliminary Study On The Relationship Between IGF-1,TNF-α And Diabetic Nephropathy In DM Rats

Objective: To explore the role of IGF-1 and TNF-αin the development of diabetic nephropathy(DN) in diabetes mellitus rats. And to provide a new method to diagnose early and therapy DN effectively.Methods: 48 Wistar rats were divided randomly into two groups. 24 rats in normal control group and 24 rats in diabetes mellitus group. The subjects in diabetes mellitus group were injected intraperitoneally with dose STZ 50mg/kg while the ones in normal control group were injected intraperitoneally with the similar dose of citric acid buffer. At 6,10 and 14 weeks, weight,fast Blood glucose and 24-hour urinary albumin excretion were observed, serum IGF-1,TNF-α,fast blood insulin were measured, the pathological changes of kidney were examined using light microscope and electron microscope. Renal expression of IGF-1 and TNF-αwere determined by immunohistoehemistry. Meanwhile,the changes of glomerular volume,GBM and immunohistoehemistry were measured by analyse morphologically.We compare these data with analysis of variance,and analyse the correlation of IGF-1 and TNF-α.Results: Compared with the control group, diabetic rats expressed more urinary albumin excretion,14 week later,it decreased but was still higher than the control group; pathohistological study revealed that there was more glomerular matrix and thicker GBM in diabetic rats(P<0.01),the volume of glomerule of diabetes mellitus group was smaller than the control group at 14 week(P<0.01);the decrease of serum IGF-1 and the increase of serum TNF-αwere observed during the whole experiment(P<0.01);immunohistochemisty showed that the expression of IGF-1 in renal tissue was much higher than normal control group(P<0.01), then they decreased continually during the whole experiment ,TNF-αprotein was seldom detectable in renal tissue from normal control group in the end of study, on the contrary, in DM group the expression of TNF-αwas increased continually during the whole experiment. There was a significant negative correlation between the expression of TNF-αand IGF-1 in renal tissue of DM group(r=-0.876,P<0.01).Conclusion: The decrease of IGF-1 and the increased of TNF-αin serum level and the expression in renal tissue may play a important role in the pathogenesy of DN. IGF-1 may play a protective role, and meanwhile TNF-αis harmful in the progression of DN.