Impact of spironolactone on the expression and activity of ROCK1 in renal tissues of uninephrectomized diabetic rats / 中华肾脏病杂志

ABSTRACT

ObjectiveTo investigate the expression and activity of Rho-associated kinase 1 (ROCK1) in renal tissues of uninephrectomized diabetic rats,and to explore the possible mechanism of renal protection of spironolactone.Methods The model rats were established by a single intraperitoneal injection of streptozotocin(STZ) after uninephrectomy and randomly divided into sham operation group(N),uninephrectomized control group?,uninephrectomized diabetic group (D),and spironolactone treated group (S).Four and 8 weeks later,biochemical indexes and renal morphology were detected.Expressions of ROCK1 and connect tissue growth factor (CTGF) were examined by immunohistochemistry and real-time PCR.Protein expression of p-MYPT1 was examined by Westem blotting.Results After 4 and 8 weeks,compared with group N and C,blood glucose,systolic blood pressure,24-h urinary protein,kidney weight/body weight (KWI) were significantly increased (P＜0.01),and extracellular matrix proliferation and basement membrane thickening were found in group D.After 8 weeks in group D,Alb significantly decreased and Scr significantly increased (P＜0.05).In group D,protein and mRNA expression of ROCK1 and CTGF increased significantly and protein expression of p-MYPT1 increased significantly as well with time.Treatment with spironolactone could partially reverse those changes. ConclusionsExpression and activity of ROCK1increase in renal tissues of uninephrectomized diabetic rats and are positively correlated with the expression of CTGF.Spironolactone can protect the kidney of diabetic rats in early stage probably through decreasing the expression of ROCK1,CTGF and inhibiting the activation of ROCK1.