| Objective:To explore the protective effect as well as its mechanism of 1,25-dihydroxyvitamin D3 on the pathological change in rats with diabetic nephropathy and different levels of transforming growth factor β1 (TGF-β1) in kidney.Methods:Diabetic nephropathy SD(Sprague Dawley, SD) rats (n=36) were classify into control and calcitriol treatment groups(n=18 rats each). Each group was divided into three subgroups based on different levels of TGF-β1 in kidney, which was induced by different virus injection. The six subgroups were called as control-H, control-M, control-L and calcitriol-H, calcitriol-M, calcitriol-L. Peanut oil and calcitriol (0.03ug·kg-1·d-1) was respectively given to control and treatment groups for 37 days. The mRNA of TGF-pi, PTEN, COLLAGEN-1, CTGF and ET-1 and proteins of TGF-β1 and ET-1 in kidney were measured by immunohistochemistry. The ultra-structure, morphology, severity of fibrosis (by HE and MASSON staining), serum creatine (SCr) and blood urea nitrogen (BUN) in control subgroups with different TGF-β1 levels were evaluated. After calcitriol intervention, the above parameters were re-evaluated.Results:(1) The levels of mRNA and protein of TGF-β1 in kidney gradually decreased in control-H, control-M, and control-L subgroups. The higher expression of TGF-β1 is associated with more severe pathological changes, more fibrosis and higher levels of SCr and BUN. (2) Calcitriol intervention significantly decreased the expression of mRNA of TGF-β1, COL-1、CTGF and ET-1 and protein of TGF-β1, ET-1, while increased the mRNA expression of PTEN (all P<0.05), accompanied by improvements in ultra-structure and HE and MASSON staining changes, fibrosis, SCr and BUN.Conclusion:(1)The higher expressions of TGF-β1 and COL-1、CTGF and ET-1 are associated with more severe diabetic nephropathy. (2)Calcitriol has some anti-fibrosis effects in diabetic nephropathy, which may be mediated by down regulation of related downstream factor expression. |
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