Protective Effects Of Rho Kinase Inhibitor On Rats’ Vascular Endothelium And Its Effects On The Expression Of ENOS

Objective To explore the protective effects of Rho kinase inhibitor(fasudil) on rats’ vascular endothelial cells and the effects on the expressionof endothelial nitric oxide synthase (eNOS).Methods Thirty Spraque-Dawley male rasts were randomly dividedinto5groups (6each): control group (intraperitoneal injection with0.9%normal saline), hyperhomocysteinemia (HHcy) group, low-dose fasudilgroup [L-treatment group, intraperitoneal injection with1mg/(kg·d) fasudil],middle-dose fasudil group [M-treatment group, intraperitoneal injectionwith5mg/(kg·d) fasudil], and high-dose fasudil group [H-treatment group,intraperitoneal injection with15mg/(kg·d) fasudil]. Animals in HHcy groupand fasudil groups were administered continuously with water containing1.5%methionine for4weeks to establish HHcy damaged vascularendothelium model, and those in control group were only fed drinking water.After successful reproduction of model, the enzymatic method was appliedto measure the serum level of nitric oxide (NO). The expressions of eNOS,Rho-associated coiled-coil protein kinase2(ROCK2) and RhoA protein inaorta were assessed by immunohistochemistry and Western blotting. Results Compared with control group, the serum NO level andexpression of eNOS protein in aorta decreased significantly in HHcy group(P＜0.05). Compared with HHcy group, the serum NO level increasedsignificantly in M-and H-treatment group (P＜0.05), but no statisticaldifference was found in L-treatment group (P＞0.05). The aortic endothelialeNOS positive cells increased significantly in H-treatment group comparedwith that in HHcy group and L-treatment group (P＜0.05), but no significantincrease in L-treatment group as compared with that in HHcy group (P＞0.05). Compared with HHcy group, the expression of RhoA and ROCK2decreased significantly in H-treatment group (P＜0.05), but no significantchange was found in L-and M-treatment group (P＞0.05).Conclusion High-dose fasudil can protect vascular endothelia byinhibiting Rho/ROCK pathway to increase the expression of eNOS and NO.