The relationship between IGF-1 and renal tubulointerstitial fibrosis in 5/6 nephrectomy rats

Objective To explore the relationship between IGF-1 and renal tubulointerstitial fibrosis in chronic renal failure(CRF) rats. Methods CRF model was induced by 5/6 nephrectomy. Sham operation was performed as control (sham group).Nephrectomy rats were randomly divided into Nx group [treated with vehicle intraperitoneally) and IGF group [treated with rhIGF-1 750 ng/(kg·d) intraperitoneally].Twelve weeks after nephrectomy,renal function,proteinuria,renal and heart weight were measured.Renal pathology and the expression of IGF-1,α-SMA,vimentin were assessed. Results ①Serum creatinine (Cr),BUN,24 h proteinuria,renal weight and heart weight in two nephrectomy groups significantly increased compared with the sham group(P0.05).Rats treated with rhIGF-1 showed higher serum Cr,BUN,24 h proteinuria, renal weight, heart weight than those in Nx group (P0.05).②The remnant kidneys showed glomerular hypertrophy and extensive glomerular damage consisting of global or segmental sclerosis and/or hyalinosis,tubular dilation,cast formation,tubular atrophy,interstitial fibrosis,as well as lymphocyte infiltration.Compared with Nx group,the glomerular sclerosis index (GSI) and tubulointerstitial index(TII) increased in rhIGF-1 treated group (P0.05).③IGF-1 strongly expressed in renal interstitium in Nx group,and was up-regulated by rhIGF-1.④α-SMA was confined to vascular smooth muscle cell in sham group,while it strongly expressed in interstitium in Nx group,particularly in scar areas.In IGF group, the expression of α-SMA up-regulated(P0.05).There was no vimentin expression in interstitium in sham group,but it strongly expressed in interstitium in Nx group,and was up-regulated by rhIGF-1. Conclusion IGF-1 may be involved in the process of the transdifferentiation of the tubulointerstitial cell to myofibroblastic cell,and induce the interstitial fibrosis and renal function injury in remnant kidney.