| Object This study was designed to determine the therapeutic effects of rapamycin on diabetic nephropathy at early stage.Methods twenty-four Sprague-Dawley (SD) rats were randomly divided into two groups: control group (group C, n=8) and diabetes group. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ).Four weeks later, the total diabetic animals were divided into diabetes nephropathy group (group DN; n= 8)and rapamycin-treated group (group DN+RAPA; n= 8). Rapamycin was administered by daily gavage for 8 weeks at 1 mg/kg per d. All rats were sacrificed at 12 weeks . Blood glucose (BG), body weight (BW), 24-h urinary albumin excretion (24hUalb), kidney weight (KW), KW/BW, glomerular tuft area (AG), glomerular tuft volume (VG), mesangial matrix expansion index(EMMI) were measured when the rats were sacrificed. The mRNA and protein levels of connective tissue growth factor(CTGF),transforming growth facter-B1(TGF-β1), fibronectin (FN) were detected by reverse-transcriptional-polymerase chain reaction (RT-PCR) and immunohistochemical staining, respectively.Results There was a significant increase of BG ,24hUalb, KW/BW in DN group compared to those in C group, DN group also had a significant increase of AG, VG and EMMI. Treatment with RAPA completely prevented the increase in 24hUalb, KW/BW and the expansion of mesangial matrix in DN+RAPA group. There was a weak expression for mRNA and protein levels of CTGF ,TGF-β1 and FN in C group, while a significant increasing expression of CTGF ,TGF-β1 and FN mRNA and protein levels was found in diabetic kidney . DN+RAPA group had a noticeable decrease of CTGF ,TGF-β1 and FN mRNA and protein expression.Conclusion Treatment with RAPA at the dose of this experiment substantially prevented the development of early stage diabetic nephropathy.
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