Effects of leflunomide on expression of transforming growth factor-β1 in focal segmental glomerulosclerosis rats

Objective To explore the possible mechanisms of the protective effect of leflunomide on kidneys by observing the effects of leflunomide on rat kidney tissue of focal segmental glomerulosclerosis (FSGS) expression level of transforming growth factor (TGF)-β1. Methods Twenty-four SD rats were randomly divided into 3 groups: normal control group (n=8), FSGS model group (n=8) and leflunomide treatment group (n=8). Unilateral nephrectomy 1 week after repeated injection of doxorubicin established FSGS model.Since 2 weeks after surgery, the treatment group had been given the leflunomide suspension 5 mg/(kg·d) orally, while normal control group and model group had been given the same amount of solvent orally.In the 8th week of the experiment, the rats were sacrificed and the specimens were collected, so serum creatinine, blood urea nitrogen, total cholesterol, albumin and 24 hours urinary protein were recorded; renal tissue was taken for pathological examination and calculation of glomerular sclerosis index (GSI) was made; immunohistochemical detection of TGF-β1 expression in the kidney was performed; The expression of TGF-β1 was examined by Western blot. Results Compared with normal control group, FSGS model group and leflunomide treatment group rats' 24 hours urinary protein excretion, serum creatinine, blood urea nitrogen, and cholesterol significantly increased while serum albumin significantly reduced severe renal pathological changes and TGF-β1 protein expression was significantly increased, and the differences were statistically significant (all P<0.05); Compared with the FSGS model group, in the 8th weekend of the experiments, the treated rats' 24 hours urinary protein excretion, relevant serum biochemical indicators of renal pathological changes had different degrees of improvement in renal tissue and TGF-β1 protein expression was decreased, so the differences above were statistically significant(all P<0.05). Conclusions Leflunomide may reduce the FSGS kidney tissue fibrosis by inhibiting the expression of TGF-β1, and thus protect the kidneys. Key words: Focal segmental glomerulosclerosis; Transforming growth factor -β1; Leflunomide; Adriamycin