Effect of Losartan on Renal Tubular Epithelial Cells Transdifferentiation in Diabetic Rats

[Objective] To observe the effect of Losartan on renal tubular epithelial cell myofibroblast transdifferentiation in diabetic rats and its possible mechanisms.[Methods]Fifty Wistar rats were randomly divided into two groups:Normal control group(n=10), Diabetic mellitus models group (n=40) which were established by intraperitoneal injection of streptozotocin (60 mg·kg~ -1 ·d~ -1 ). After these models were successfully established,they were randomly divided into two groups :diabetic group without therapy and diabetic group with Losartan (20 mg·kg~ -1 ·d~ -1 ). At eight and sixteen weeks after therapy with Lorsartan, the excretion of urinary protein and serum creatine were measured. Alpha smooth muscle actin(α-SMA), vimentin and transforming growth factor-β1(TGF-β1) in renal tubular epithelial cells were detected by immunohistochemistry of SP method. [Results]①The excretion of urinary protein in diabetic group was significantly higher than that in control and Losartan therapy groups. The tubulointerstitial injury and the accumulation of extracellular matrix protein in diabetic models were obvious. ②Compared with normal control group, α-SMA, vimentin and TGF-β1 in renal tubular epithelial cells showed gradually stronger positive in diabetic group (P0.01). ③In comparison with diabetic group, Lorsartan could reduce excretion of urinary protein and delay the progression of tubulointerstitial fibrosis in diabetic rats, down-regulated the expression of α-SMA, vimentin and TGF-β1 in renal tubular epithelial cells (P0.01).[Conclusion]①Renal tubular epithelial-myofibroblast transdifferentiation is an important event in the progress of diabetic nephropathy, which may be up-regulated by transforming growth factor-β1.②Losartan may down-regulate expression of α-SMA, vimentin and TGF-β1 in diabetic renal tubular epithelial cells, can restrain the procession of epithelial-myofibroblast transdifferentiation. ③Losartan restraining the procession of epithelial-myfibroblast transdifferentiation may be a mechanism of protective effect on diabetic nephropathy.