Effects And Mechanism Of Candesartan In Atherosclerosis Rats

Objects:To investigate the anti-atherosclerosis effects and mechanism of Candesartan on experimental atherosclerosis rats.Methods:Male SD rats of ten-months were randomly divided into 5 groups:A(normal rats),B(atherosclerosis rats),C(atherosclerosis rats fed with candesartan 1 mg.kg-1.d-1), D(atherosclerosis rats fed with candesartan 5 mg.kg-1.d-1) and E(atherosclerosis rats fed with candesartan 10mg.kg-1.d-1). The rats of group B,C,D,E were fed with high lipid feedstuff and received intraperitoneal injection of vitamin D3 at one time. The rats of group A were fed with nomal feedstuff and injected the saline with the same dose. Candesartan was given to the rats of group C,D,E by gavage from the beginning to the end of the experiment. At the same time rats of groupA and B were given the saline of same dose by gavage. After 12 weeks,the same arteries of rats of each group were examined by HE staining and electron microscope.The lipid indexes, MDA and SOD were determined by biochemistry method.OxLDL in serum of each group rats was measured by ELISA. The expressions of MMP-2 and VEGF in aorta were determined by immunohistochemistry.Result:1 The TG in groupC,D and E was lower than those in group B without a dose-dependent manner(P<0.05,P<0.01).Compared with groupB,HDL increased significantly( P< 0. 05) in the group E. The TG / HDL in the group E decreased significantly( P< 0. 05).2 Compared with groupA, morphological changes of Atherosclerosis in the arteries of group B were observed.Compared with group B, morphological changes of atherosclerosis of groupC,D and E lightened significantly.3 Compared with group A,the MDA and SOD were significantly different in the group B ( P<0.01).The MDA in group E was lower than those in the group B ( P<0.01).Compared with group B, SOD increased significantly( P< 0. 05) in the group E.4 The oxLDL in groups of C,D and E were lower than those in group B without a dose- dependent manner(P<0.01).5 Compared with group B, the expressions of MMP-2 in aorta decreased in groups of D and E(P<0.05). Compared with group B, the expressions of VEGF in aorta decreased in groups of C,D and E(P<0.05).Conclusion:1 Candesartan can regulate the disorder of blood lipids and influence the morphology of artery in atherosclerosis rats.2 Candesartan can increase SOD and decrease MDA and oxLDL remarkably of blood serum in atherosclerosis rats.3 Candesartan appeares to markedly reduce the expressions of MMP-2 and VEGF of aorta in atherosclerosis rats.