The Effect of Leflunomide on Renal Expression of TGF-β_1 in Rats With 5/6 Nephrectomy

Objective:To investigate the effects of leflunomide on the expression of TGF-β1 in rats with 5/6 nephrectomy.Methods:Rats were randomly divided into surgery group and pseudo-surgery group(group A).3 days after operation,those with 5/6 renal ablation were divide into modal group(group B)and Leflunomide treated group(group C).6 rats of each group were randomly chosen to be sacrificed at the end of the 4th and the 9th week.Samples were collected,including serum creatinine,blood urea nitrogen,cholesterol,triglyceride,24-hour urinary protein excretion.Renal TGF-β1 mRNA expression was measured with reverse transcriptase-polymerase chain reaction(RT-PCR).TGF-β1 was measured with immunohistochemical techniques.Results:(1)Compared with group A,the blood urea nitrogen,serum creatinine and lipid didn't change in group B at the end of 4th week after the animal modals of 5/6 nephrectomy were established successfully(P0.05),but 24-hour urinary protein excretion and renal TGF-β1 mRNA expression were increased significantly(P0.01)while serum albumin was decreased significantly(P0.01)in group B.Those changes were more severe at the end of the 9th week.(2)Compared with group B,serum creatinine,blood urea nitrogen,cholesterol,24-hour urinary protein excretion and renal TGF-β1 mRNA expression were decreased(P0.05)at the end of the 9th week in group C.TGF-β1 could also be observed in mesangial area by immunohistochemical techniques in group B.In group C these changes alleviated.Conclusion:Leflunomide can decrease the 24-hour urinary protein excretion,correct the lipid metabolism disorder,and lessen the sclerosis of kidney in the 5/6 nephrectomic rats The mechanism might be related with that leflunomide down-regulating the synthesis and activity of TGF-β1 mRNA.