Effects of Rho-kinase inhibitor on endothelail function in rats with hyperglycaemia and h yperlipid / 医学研究生学报

ABSTRACT

Objective Hyperglycaemia and hyperlipid are common in clinical cardiovascular disease .The article was to ob-serve the change of endothelial and the expression of Rho-kinase in the aorta of rats with hyperglycaemia and hyperlipid and the rela-tionship between them .Methods Healthy male Wistar rats were randomly divided into 3 groups5 as normal control group , 10 as model group and 10 as drug intervention group .The latter two groups were given high-fat diets for 5 weeks after tail vein injection of streptozocin (STZ) to establish hyperglycaemia and hyperlipid models , then fasudil (inhibitor of Rho-kinases) or saline were respec-tively given intraperitoneally for 4 weeks.Venous blood glucose (VBG), blood lipid levels, ET-1 and eNOS were tested, along with the expression of MYPT-1(the protein substrates of ROCK)、mRNA of RhoA and ROCK. Results Compared with normal control group, the levels of VBG、ET-1、MYPT-1、mRNA of ROCK and Rho A were increased in model group[(6.18±1.14)mmol/L vs (26.36± 3.25)mmol/L,(72.13±6.13 )pg/mL vs (88.22±4.61) pg/mL, (0.54±0.08) v s (1.28±0.17),(0.16±0.20) vs (0.83± 0.12),(0.40±0.18) vs (0.78±0.13),P<0.05].TG、TC、LDL were also higher in model group(P<0.05), while eNOS level was lower in model group than in control group[(24.42±2.13)U/L sv (17.36±1.58)U/L,P<0.05].Compared with model group, the levels of VBG[(17.70±2.69)mmol/L]、TG、TC、LDL, ET-1 [(75.03±2.50)pg/mL]、MYPT-1(0.74±0.01)、mRNA of ROCK(04.0±0.08) and Rho A (0.25±0.07)in drug intervention group were lower(P<0.05), while eNOS level (0.74±0.11) was higher(P<0.05) in drug intervention group than in model group . Conclusion Endothelial dysfunction and over-expression of Rho kinase can be found in hyperglycaemia and hyperlipid rat models .Fa-sudil could improve endothelial function .