| Objective: To explore the mechanism of renal protective effect of Simvastatin in diabetic rat kidney .And to offer a theoretical proof in the clinical application.Methods: Inbreeding, clean-54 male Wistar rats, weighing 190-230g, were randomly divided into control group(NC, n=18), diabetes mellirus group(DM, n=18) and Simvastatin intervention group(S, n=18). After 12 hours fasting, the rats in Group DM and Group S were performed peritoneal injection of streptozotocin(STZ) 55mg/kg and the rats in Group NC were performed injection of citric acid buffer with the equal volume. 72 hours later, the rats in Group S and Group DM whose blood glucose was above 16.7mmol/L three consecutive days were identified as modeling success, whereas those in Group S and Group DM whose blood glucose was less than 16.7mmol/L were exclude. One week later, the rats in Group S were treated with 2mg/kg simvastatin by daily gavage while the ones in Group DM and Group NC were received equal volume normal saline by daily gavage. At 4,8 and 12 weeks, weight,fast Blood glucose and 24-hour urinary albumin excretion were observed, serum P-selectin,BUN and Cr were measured, the pathological changes of kidney were examined by light microscope and the expression of P-selectin were detected by immunohistochemistry and image analysis system.Results:1. After 72 hours of STZ injection, compared with Group NC, blood glucose in Group DM and Group S were significantly higher (P<0.05). Fasting serum insulin in Group DM and Group S were significantly lower than that in Group NC (P<0.05)2. At4, 8and12 week, compared with Group NC, the quantity of 24-hour urinary protein of the rats in Group DM and Group S was much higher. The quantity of 24-hour urinary protein of the rats in Group S was much lower than that in Group DM. With the extension of the course, the quantity of 24-hour urinary protein of the rats in Group DM increased while the one in Group S reduced.3. Under light microscope, we could observed the structure of nephridial tissue in Group NC was normal. Furthemore we could see increased volume of glomeruli of the rats in the early stage, thickness of base membrane and renal tubular epithelial cell vacuolar degeneration in Group DM. In Group S, those pathological changes alleviated. At 12 week we can't see glomerulosclerosis. After the treatment of Simvastatin the pathology in renal was improved.4. Compared with Group NC, the serum P-selectin of the rats in Group DM and Group S was much higher. The serum P-selectin of rats in Group S was much lower than that in Group DM. 5. Immunohistochemistry showed that the rats in Group NC had a small amount of glomerular P-selectin expression. There was no expression in tubular. Compared with Group NC, P-selectin expression in the renal tissue of Group DM and Group S were highter than those of Group S. Compared with Group DM, the expression of P-selectin in Group S was significantly lower.Conclusion: P-selectin was appearance in the prophase of diabetic nephropathy and it has positive correlation with the excretion of urinary albumin. Simvastatin could reduce the expression of P-selectin of diabetic rats. Then simvastatin protect the kidney through relieve the inflammatory reaction, microthrombus and urinary albumin in diabetic rats.
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