摘要
目的研究辛伐他汀对急性心肌梗死(AMI)后血管生成素-1(Ang-1)及内皮型一氧化氮合酶(eNOS)的表达调控与其促血管新生作用的关系。方法健康成年SD大鼠60只,随机分为假手术组、对照组、辛伐他汀组、辛伐他汀+L-NAME(NOS抑制剂)组、辛伐他汀+AMG386(Ang-1抑制剂)组;结扎大鼠冠状动脉左前降支建立急性心肌梗死动物模型。术后2 d分别给予辛伐他汀[1 mg/(kg.d)],辛伐他汀+L-NAME[40 mg/(kg.d)],辛伐他汀+AMG386[10 mg/(kg.wk)],均为2周,以CD31染色新生血管并检测新生血管密度;以Western blot及RT-PCR检测缺血区心肌Ang-1、eNOS、丝氨酸1177磷酸化内皮型一氧化氮合酶(p-eNOS)的表达。结果(1)辛伐他汀使AMI后缺血区心肌新生血管密度显著增加(P<0.05),而L-NAME、AMG386则显著抑制了辛伐他汀的促心肌血管新生作用(P<0.05)。(2)辛伐他汀使AMI后缺血区心肌Ang-1、eNOS、p-eNOS表达均显著增强(P<0.05),而AMG386显著抑制辛伐他汀上调p-eNOS表达的作用(P<0.05)。结论辛伐他汀促心肌血管新生作用可能与其上调Ang-1、eNOS的表达及促进eNOS磷酸化有关,其中eNOS磷酸化可能是介导Ang-1促血管新生作用的下游机制。
Objective To investigate the roles of angiopoietin-1（Ang-1） and endothelial nitric oxide synthase（eNOS） in pro-angiogenic effect of simvastatin after experimental acute myocardial infarction（AMI）.Methods Sixty healthy adult SD rats were randomly divided into the sham operated group、control group、simvastatin group、simvastatin plus L-NAME（inhibitor of NOS）group and simvastatin plus AMG386（inhibitor of Ang-1）group;Left anterior descending coronary underwent permanent occlusion to establish the AMI model.Rats with AMI were administered simvastatin[1 mg/（kg·d）],simvastatin plus L-NAME[40 mg/（kg·d）]and simvastatin plus AMG386[10 mg/（kg·wk）] respectively for 2 weeks.New microvessels in the ischemic area near the infarction myocardium were stained by CD31 and the density of new microvessels was dedected;Ang-1,eNOS and phosphoralated endothelial nitric oxide synthase at Ser1177（p-eNOS）were evaluated by Western blot and RT-PCR assay.Results（1）Simvastatin significantly increased the density of new microvessels（P0.05）,but L-NAME and AMG386 siglificantly inhibited the proangiogenic effect of simvastatin（P0.05）.（2）Simvastatin significantly improved the expression of Ang-1,eNOS andp-eNOS（P0.05）,and AMG386 significantly decreased simvastatin induced upregulation of p-eNOS.ConclusionThe proangiogenic effect of simvastatin is associated with increased expression of Ang-1,eNOS and p-eNOS,and phosphoralation of eNOS maybe the downstream pathway for Ang-1 induced angiogenesis.
出处
《基础医学与临床》
CSCD
北大核心
2010年第10期1066-1071,共6页
Basic and Clinical Medicine
基金
重庆市自然科学基金[渝发科技字(2004)54号文]
