[Inhibition of leflunomide active metabolite A771726 on high glucose-induced podocyte apoptosis].

To explore the therapeutic effects of leflunomide metabolite A771726 on high glucose-induced podocyte injury and understand its mechanism. The conditionally immortal human glomerular podocytes were divided into normal glucose group (NG), high glucose group (HG), mannitol group (MA), high glucose with SB202190 (a p38MAPK inhibitor) group and high glucose with active leflunomide metabolite A771726 group. The levels of p38MAPK and p-p38 protein were determined by Western blot. And the rate of podocyte apoptosis was evaluated by flow cytometry. (1) Podocytes with high glucose could activate the p38MAPK signaling pathway. The p-p38 protein expression was significantly elevated. Little activation of the pathways was observed in Groups NG and MA. As compared to HG, the p-p38 protein expression was significantly lowered in SB202190 and A771726 groups. (2) Apoptosis increased in podocytes with high glucose after 24 h. The apoptotic rate of group HG was the most dramatic at 48 h (18.6 ± 0.7)%. It was significantly higher than those of Groups NG and MA. The group of high glucose with SB202190 and high glucose with active leflunomide metabolite A771726 could reduce the podocyte apoptosis by 26% and 17% respectively versus the HG group. And the difference was statistically significant. Leflunomide can inhibit high glucose-induced podocyte apoptosis. And this effect may be involved in its inhibition of activation of p38MAPK.