大鼠血管损伤性重塑过程中粘着斑激酶表达和活化与替米沙坦的干预(英文)  

Interventional effect of telmisartan on expression and activation of focal adhesion kinase during vascular-injured remodeling in rats

作　　者：程芳洲[1,2] 鲍翠玉[3] 彭绩[1] 柯俊[4] 

机构地区：[1]深圳市慢性病防治院 [2]咸宁医学院附属医院心内科,湖北省咸宁市437100 [3]咸宁医学院附属医院心内科 [4]华中科技大学同济医学院附属同济医院心内科

出　　处：《中国组织工程研究与临床康复》2007年第41期8401-8403,共3页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：湖北省科技厅资助项目(2005ABA086)~~

摘　　要：背景:血管内皮损伤后,血管平滑肌细胞的粘附迁移、血管壁的增生性重塑在经皮腔内冠状动脉成形术后再狭窄发生过程中起重要作用,而在此过程中常伴有粘着斑激酶的表达和磷酸化激活。目的:观察血管紧张素受体拮抗剂替米沙坦对血管损伤性重塑及此过程中粘着斑激酶表达、活化的影响。设计:随机对照动物实验。单位:深圳市慢性病防治院,咸宁医学院附属医院心内科,华中科技大学同济医学院附属同济医院心内科。材料:实验于2005-03/05在武汉同济医院心血管实验室完成。雄性Wistar大鼠36只,体质量300～360g,随机分为对照组、模型组、治疗组,每组12只。方法:建立大鼠主动脉内皮剥脱术后再狭窄模型,模型组、治疗组大鼠以球囊导管法剥脱血管内皮。对照组及模型组正常进食及饮水,治疗组在进食同时给予替米沙坦药液5mg/(kg·d)。连续给药30d后取损伤部位血管段进行形态学观察及提取RNA和蛋白质,RT-PCR测定粘着斑激酶的mRNA表达,蛋白免疫印迹法测定粘着斑激酶的蛋白总量和磷酸化蛋白含量。主要观察指标:损伤部位血管段血管壁增生程度;给药30d后损伤部位血管粘着斑激酶的mRNA表达、蛋白总量和磷酸化蛋白含量。结果:纳入大鼠36只,均进入结果分析。术后30d,模型组主动脉内膜明显增厚,粘着斑激酶mRNA水平明显增高,蛋白含量及磷酸化水平均明显较对照组增加,而治疗组血管内膜增生程度明显减轻,粘着斑激酶mRNA表达活性明显降低,粘着斑激酶蛋白含量及磷酸化水平明显较模型组降低。结论:替米沙坦可明显减轻大鼠血管内膜剥脱术后血管内膜增生程度,抑制血管损伤后粘着斑激酶表达与活化。替米沙坦的抗血管损伤性重塑作用可能与抑制粘着斑激酶表达与活化有关。BACKGROUND ： Adherent migration of vascular smooth muscle cells and proliferated remodeling of vessel walls following vascular endothelial injury play a key role in onset of restenosis after percutaneous transluminal coronary angioplasty, while expression and phosphorylation activation of focal adhesion kinase are attacked during this period. OBJECTEVE： To observe the interventional effect of angiotensin receptor antagonist, telmisartan, on the expression and activation of focal adhesion kinase during vascular-injured remodeling. DESIGN ： Randomized controlled animal study SEI-rING： Shenzhen Center for Chronic Disease Control and Prevention; Department of Cardiology, Affiliated Hospital of Xianning Medical College; Department of Cardiology, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology. MATERIALS： The experiment was carried out in the Cardiovascular Laboratory, Wuhan Tongji Hospital from March to May 2005. A total of 36 male Wistar rats weighing 300-360 g were randomly divided into control group, model group and treatment group with 12 in each group. METHODS ： Aortal restenosis models were established after endothelial denudation. Foley＇s tube technique was used to strip vascular endothelium of rats in the model group and the treatment group; while, rats in the control group and the model group were fed and drunk normally; in addition, rats in the treatment group were also given 5 mg/ （kg·d） telmisartan solution. Thirty days after successive administration, vessels at injured sites were collected to observe the morphological changes and extract RNA and protein. Reverse transcriptase polymerase chain reaction （RT-PCR） was used to measure mRNA expression of focal adhesion kinase and Western blot technique was used to measure total protein and phosphorylated protein of focal adhesion kinase. MAIN OUTCOME MEASURES： Proliferation of vessel wall at injured sites; mRNA expression, total protein and phosphorylated protein of focal adhesion kin

关 键 词：替米沙坦 粘着斑激酶 内皮剥脱术 血管重塑 

分 类 号：R54[医药卫生—心血管疾病]