The Protective Effects Of Leflunomide On Iga Nephropathy Accompanied By Vasculopathy In Rats

Background and objective:IgA nephropathy(IgAN) is the most commonly kidney disease in our country, the vasculopathy is very common in IgAN, it has been showed to be closely correlated with glomerular sclerosis and renal interstitial fibrosi and played an important role in the progression of IgAN.But now there has not a suitable model to inquire the mechanism of vasculopathy compaired with IgAN. So we constructed the rat model of IgAN with BSA+LPS+CCL4,and induced vasculopathy by high fat diet. Compaired with simvastatin,we observed the effect of leflunomide on vasculopathy and approach the possible machnism.Methods:1.36SD rats were randomly divided into control group,IgAN group and model group, each group had12rats. Each rat in IgAN group, model group was induced by BSA+LPS+CCL4for8weeks,at the same time, the model group was given high fat diet and intraperitoneal inject vitamin D3.The general status, hematuria, proteinuria,serum biochemistry index and histological damage were measured at week4,8,10.2.60SD rats were randomly divided into control group,model group,simvastatin group and leflunomide group. The general status,proteinuria,serum biochemistry and histological damage were measured at week4,8,10. Additionally,we detected the expression of monoeyte chemoattractant protein(MCP-1), vascular cell adhesion factor(VCAM-1) by immunohistochemistry and RT-PCR.Results:1. At week10,compared with control group and IgAN group,24h urinary protein、TG、TC、HDL、LDL、Ca、Cr was increased gradually in model group (P>0.05), and TP、ALB were decreased (P>0.05). IgA deposited along the glomerular mesangial by immunofluorescence. From the eighth week, the renal artery wall was thicking and the lumen was shrinking.Compaired to IgAN group,the integral of glomerular, tubulointerstitial and vascular lesions was significantly higher (P<0.05).2.Compared with model group, Each treated group showed gradually decreased in24h urinary protein、TG、TC、HDL、LDL、Ca、Cr and gradually increased in TP、ALB (P<0.05) at week10, while tubulointerstitial and vascular histologieal damage were lower (P<0.05). The expression of MCP-1and VCAM-1was down regulated(P<0.05). Compared with simvastatin, leflunomide significantly reduced the scores of vascular and tubulointerstitial histologieal damage, while the expression of MCP-1and VCAM-1(P<0.05).Conclusion1. IgAN vasculopathy was seted up by giving high fat diet on IgA nephropathy rat.2. Leflunomide could reduce the lesions of renal vascular, glomcrulus and tubulointerstitial, while the expression of MCP-1and VCAM-1.It suggested that leflunomide could reduce the renal vasculopathy and delay the renal interstitial fibrosis by inhibiting inflammatory responselesions.Compared with simvastatin, leflunomide played an greater effect on renal protective.