| Objective: To investigate the effects of atorvastatin on expression of osteopontin in diabetic rats kidney and its regulation mechanism. Methods: 45 rats were divided into 4 groups affer they were feed one week, which were normal group, higt fat group, diabetic group and atorvastatin group. The normal group rats were feed normol diet. The diabetic group and the atorvastatin group rats were treated with streptozotocin by intraperitoneal injection(35mg/kg) after they were given 8-week's high fat diet. After a week, the atorvastatin group rats were give atorvastatin 20mg/(kg?d). The blood and kidney were obtained after 8 weeks, serum glucose, triglyceride, cholesterol were analyzed. The renal pathologic injury was observed by HE stains. The expression of OPN and pp38 were detected by Western blot and immunohistochemical methods. The MDCK cells were stimulated with high-glucose DMEM(25mM glucose). At the same time, different consistency atorvastatin were used to stimulate the cell for 48 hours. After that, it was observed that change of OPN expression and p38 phosphorylation levels. Results The diabetic rats model was established successfully. Compared with normal group, serum glucose and cholesterol were significantly increased ( P <0.05, P <0.05) in diabetic group. Compared with diabetic group rats , serum cholesterol was significantly decreased (P <0.05). HE stains shows that DM rats has renal damege characterized by glomerular hypertrophy, mesargial regin, mild expansion of the mesangial matrix, and the renal capsule present a narrow fracture, compared with the normal group and the atorvastatin group. The tubule of diabetic group showed slight hypertrophy and apparent hydrops, and serious vacuolar degeneration. Inflammatory cell infiltration could be detected in tubule interstitial substance. The damege were released in atorvastatin group. Osteopontin's expression is localized in nephric tubule epithelial cell in this study. The section with the anti-osteopontin showed a strong nucler positive signal in diatetic group. The osteopontin's positive rate was significationly reduced in atorvastatin group. Atorvastatin markedly decreased cholesterol and kidney pathology damage. The expression of osteopontin and pp38/p38 was obviousily increased in diabetic group(P < 0.05), compared with normal group. And the immunohistochemistry and western blot results show that the reduction of expression of OPN and pp38 was significant compared with the diabetic group(P<0.05). In MDCK cells cultured in 25mM glucose DMEM, the expression of osteopontin wsa increased , compared with normal group(P<0.05). Which was decreased treated with atorvastatin compared with high glucose group(P<0.05). Conclusion Atorvastatin could decreased the level of Serum cholesterol and protect the kidney. Atorvastatin decreased the expression of osteopontin and pp38/p38 in diabetic rats renal. Atorvastatin maybe decrease the expression of osteopontin via p38/MAPK pathway. |
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