protective effects of rho kinase inhibitor on rats’ vascular endothelium and its effects on the expression of eno
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2012
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Abstract
Objective To explore the protective effects of Rho kinase inhibitor (fasudil) on rats' vascular endothelial cells and the effects on the expression of endothelial nitric oxide synthase (eNOS). Methods Thirty male SD rats were randomly divided into 5 groups (6 each): control group (intraperitoneal injection with 0.9% normal saline), hyperhomocysteinemia (HHcy) group, low-dose fasudil group [L -treatment group, intraperitoneal injection with 1mg/(kg•d) fasudil], middle-dose fasudil group [M-treatment group, intraperitoneal injection with 5mg/(kg•d) fasudil], and high-dose fasudil group [H-treatment group, intraperitoneal injection with 15mg/(kg•d) fasudil]. Animals in HHcy group and fasudil groups were administered continuously with water containing 1.5% methionine for 4 weeks to establish HHcy damaged vascular endothelium model, and those in control group were only fed drinking water. After successful reproduction of model, the enzymatic method was applied to measure the serum level of nitric oxide (NO). The expressions of eNOS, Rho-associated coiled-coil protein kinase 2 (ROCK2) and RhoA protein in aorta were assessed by immunohistochemistry and Western blotting. Results Compared with control group, the serum NO level and expression of eNOS protein in aorta decreased significantly in HHcy group (P < 0.05). Compared with HHcy group, the serum NO level increased significantly in M-and H-treatment group (P < 0.05), but no statistical difference was found in L-treatment group (P>0.05). The aortic endothelial eNOS positive cells increased significantly in H-treatment group compared with that in HHcy group and L -treatment group (P < 0.05), but no significant increase in L-treatment group as compared with that in HHcy group (P>0.05). Compared with HHcy group, the expressions of RhoA and ROCK2 decreased significantly in H-treatment group (P < 0.05), but no significant change was found in L-and M-treatment group (P>0.05). Conclusions High-dose fasudil can protect vascular endothelia by inhibiting Rho/ROCK pathway to increase the expression of eNOS and NO.
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wu2012medicalprotective
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| Authors | ;Qiao WU;Kang-hua MA;Xiao-gang ZHANG;Qian DONG;Xiao-feng LAI |
| Journal | frontiers in neurorobotics |
| Year | 2012 |
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