摘要
目的探讨Rho激酶抑制剂-法舒地尔对大鼠动脉粥样硬化的防治作用及其相关机制。方法以普通饮食喂养大鼠作为对照组(n=10);链脲佐菌素诱导的糖尿病大鼠内膜损伤存活后,高脂饮食8周,分为动脉硬化组、瑞舒伐他汀组及法舒地尔组(n=10),继续高脂饮食4周,药物干预2个月,行血脂、血管细胞黏附分子-(lVCAM-1)、细胞间黏附分子-(lICAM-1)及Rho激酶mRNA检测。结果与对照组相比,动脉硬化组大鼠血脂增高,VCAM-1、ICAM-1及Rho激酶mRNA表达增加(P<0.05);与动脉硬化组对比,瑞舒伐他汀组各指标均改善,而法舒地尔组除对血脂无明显影响外,与瑞舒伐他汀具有相似的抗动脉粥样硬化作用(P<0.05)。结论法舒地尔具有抗动脉粥样硬化作用,其机制可能在于通过干预Rho/Rho激酶信号通路表达,抑制动脉内皮的炎症反应。
【Objective】 To investigate the effects of fasudil on atherosclerosis and Rho kinase expression in hypercholesterolemic diabetic rat model,and to observe its action mechanism.【Methods】Forty Wistar rats were randomly divided into four groups： control group,atherosclerosis group,simvastatin group and fasudil group（10 in each）.The atherosclerosis group,simvastatin group and fasudil group were fed with high cholesterol diet for 12 weeks.After feeding drug for 2 months,VCAM-1,ICAM-1 and Rho kinase mRNA were measured by reverse transcription polymerase chain reaction analysis（RT-PCR）.【Results】 HE staining showed that atherosclerotic and luminal structure changes in aorta in atherosclerosis group were more obvious as compared with the control group.Plasma lipid and the expression of mRNA of VCAM-1,ICAM-1 and Rho kinase in atherosclerosis group were also significantly higher than those in control group（P 0.05）.Compared with atherosclerosis group,HE staining results were better in simvastatin group and fasudil group.The expression of mRNA of VCAM-1,ICAM-1 and Rho kinase in simvastatin group and fasudil group were decreased.Fasudil had similar anti-atherogenetic effects with simvastatin but had no influence on plasma lipid（P 0.05）.【Conclusion】Fasudil could attenuate atherosclerosis in this hyperchololesterolemic diabetic rat model which might attribute to its anti-inflammatory effects induced by Rho/Rho kinase signal transduction pathway.
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2010年第6期805-809,共5页
China Journal of Modern Medicine
基金
沈阳市科学计划项目资助(No:070178)
