Abstract:

Objective   To investigate the effect and possible mechanism of mycophenolate mofetil(MMF) on renal tubular epithelial mesenchymal transition in diabetic rats. Methods      Twenty-eight male SD rats were randomly divided into the normal control group (group N, n=8), the diabetes mellitus group (group DM) and diabetes mellitus treated with MMF group(group M, n=10). The diabetes mellitus model was constructed by streptozotocin (STZ) injection. Blood glucose, body weight, kidney weight/body weight, 24h urinary protein, serum creatinine and the pathological morphological change of renal tubulo-interstitial damage were detected after 12 weeks. Immunohistochemistrcal staining and Western blot were conducted to detect expressions of α-SMA and TGF-β1 in renal tissues. Results   There was a significant difference between group N and group DM in the levels of blood glucose, kidney weight/body weight, 24h urinary protein, serum creatinine and tubulo-interstitial damage index(TII) (P<0.01). All the parameters significantlydecreased in group M compared with group DM (P<0.01), except for the levels of blood glucose and body weight(P>0.05). Immunohistochemical staining showed that expressions of α-SMA and TGF-β1 in renal tubular cells were higher in group DM compared with group N(P<0.01). But expressions of α-SMA and TGF-β1 in group M were significantly lower compared with group DM( P<0.01). Western blot showed that expressions of α-SMA and TGF-β1 in renal tissue of group DM were increased by 3.4 and 1.1 times compared with the group N, and were reduced by 55% and 40% in group M (P<0.01).Conclusion   MMF can down-regulate expressions of αSMA and TGF-β1 in diabetic renal tubular epithelia, prevent the process of epithelial trans-differentiation in diabetic mellitus models, and play a protective role in diabetic nephropathy.

Key words: Diabetic nephropathy; Mycophenolate mofetil; Epithelial mesenchymal transition; α-smooth muscle actin; Transforming growth factor-beta 1