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J Diabetes Res. 2013;2013:174526. doi: 10.1155/2013/174526. Epub 2013 Dec 1.

Benidipine protects kidney through inhibiting ROCK1 activity and reducing the epithelium-mesenchymal transdifferentiation in type 1 diabetic rats.

Wu G1, Xu M2, Xu K2, Hu Y3.

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Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning 437100, China ; Department of Medicine, Clinic Medical College of Hubei University of Science and Technology, Xianning 437100, China.
Department of Medicine, The Second Affiliated Hospital of Hubei University of Science and Technology, Xianning 437100, China.
Department of Immunology, Wuhan University of Science and Technology, Wuhan 430081, China.


We investigated the protective effect of benidipine, by testing the changes of the activity of Rho kinase and transdifferentiation of renal tubular epithelium cells in vivo. Wistar rats were randomly divided into two groups: normal (N) and diabetes. STZ were used to make the rats type 1 diabetic and were randomly assigned as diabetes without treatment (D), diabetes treated with benidipine (B), and diabetes treated with fasudil (F) and treated for 3 months. Immunohistochemistry and western blotting were for protein expressions of ROCK1, α-SMA, and E-cadherin and real-time PCR for the mRNA quantification of ROCK1. Compared with N group, D group had significant proliferation of glomerular mesangial matrix, increased cell number, thickened basement membrane, widely infiltrated by inflammatory cells and fibrosis in the renal interstitial, and dilated tubular. Those presentations in F and B groups were milder. Compared with N group, D group showed elevated MYPT1 phosphorylation, increased expression of ROCK1, α-SMA protein, and ROCK1 mRNA and decreased expression of E-cadherin protein. B group showed attenuated MYPT1 phosphorylation, decreased ROCK1, α-SMA protein, and ROCK1 mRNA expression and increased expression of E-cadherin protein. In conclusion, benidipine reduces the epithelium-mesenchymal transdifferentiation and renal interstitial fibrosis in diabetic kidney by inhibiting ROCK1 activity.

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