Mechanism Of Proteinuria Prevention By 1,25-(OH)₂D₃ Analogs In Diabetic Nephropathy Rats

Objective To study the effects of 1,25- (OH)₂ D₃ analogs paricalcitol on the level of renin ,the expression of heparanases (HPA) and podocin protein and mRNA in the kidney of diabetic nephropathy (DN) rats and its possible mechanism.Methods DN model rats were established by intraperitoneal injection with streptozotocin(STZ). All the DN rats were randomly divided into the paricalcitol group (group P), the losartan group (group T), the combination of paricalcitol and losartan group (group L), the DN group (group D) and the health control (group N) was also established. Group P were treated with 0.05μgï¹’kg^-1ï¹’d^-1 of paricalcitol by gavage;Group T were 10mgï¹’kg^-1ï¹’d^-1 losartan by gavage; Group L were treated with the combination dose of Group P and Group T; Group D and Group N were given equal amount of peanut oil by gavage. 24-h urinary protein and serum biochemical indicators were examined after 12 weeks. ELISA methods were applied to detect the concentration change of renin and Angâ…¡in the kidney, Immunohistochemistry and RT-PCR methods were applied to detect the protein and mRNA expression of HPA and podocin.Results Compared with Group D , 24-h urinary protein, renin and Angâ…¡of Group P, T and L were markedly decreased, Group L was significantly lower than Group P and Group T in 24-h urinary protein (P<0.05). Compared with Group D, the expression of HPA mRNA and protein in Group P, T and L were markedly decreased, Group L were significantly lower than Group P and Group T (P<0.05). Compared with Group D, the expression of podocin mRNA and protein in Group P ,T and L were markedly increased, and they were significantly higher in Group L (P<0.05). There was direct correlation between renin and HPA expression (r=0.78 P<0.05) and inverse correlation between renin and podocin protein expression (r=-0.63 P<0.05).Conclusion Paricalcitol can significantly reduce the proteinuria, which may be associated with inhibiting the renin by down-regulate protein expression of HPA of glomerular basement membrane and up-regulate the protein expression of podocin of podocyte. Combination of 1,25- (OH)2 D3 analogs and angiotensinâ…¡receptor blocker have better effective and renal protection than single-agent therapy in reduce the proteinuria.