CAJ | 학술논문

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Wiser大鼠36只.体质量300～360 g,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5 mg/(kg·d).连续给药30 d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30 d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:纳人大鼠36只,均进人结果分析.术后30 d,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.
배경:혈관내피손상후,혈관평활기세포적점부천이、혈관벽적증생성중소재경피강내관상동맥성형술후재협착발생과정중기중요작용,이재차과정중상반유점착반격매적표체화린산화격활.목적:관찰혈관긴장소수체길항제체미사탄대혈관손상성중소급차과정중점착반격매표체、활화적영향.설계:수궤대조동물실험.단위:심수시만성병방치원,함저의학원부속의원심내과,화중과기대학동제의학원부속동제의원심내과.재료:실험우2005-03/05재무한동제의원심혈관실험실완성.웅성Wiser대서36지.체질량300～360 g,수궤분위대조조、모형조、치료조,매조12지.방법:건립대서주동맥내피박탈술후재협착모형,모형조、치료조대서이구낭도관법박탈혈관내피.대조조급모형조정상진식급음수,치료조재진식동시급여체미사탄약액5 mg/(kg·d).련속급약30 d후취손상부위혈관단진행형태학관찰급제취RNA화단백질,RT-PCR측정점착반격매적mRNA표체,단백면역인적법측정점착반격매적단백총량화린산화단백함량. 주요관찰지표:손상부위혈관단혈관벽증생정도;급약30 d후손상부위혈관점착반격매적mRNA표체、단백총량화린산화단백함량.결과:납인대서36지,균진인결과분석.술후30 d,모형조주동맥내막명현증후,점착반격매mRNA수평명현증고,단백함량급린산화수평균명현교대조조증가,이치료조혈관내막증생정도명현감경,점착반격매mRNA표체활성명현강저,점착반격매단백함량급린산화수평명현교모형조강저.결론:체미사탄가명현감경대서혈관내막박탈술후혈관내막증생정도,억제혈관손상후점착반격매표체여활화.체미사탄적항혈관손상성중소작용가능여억제점착반격매표체여활화유관.
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.OBJECTIVE: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.SETTING: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 carded 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 endothetium 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 clays 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 Westem blot technique was USod 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 kinase at injured sites at 30 days after administration.RESULTS:A total of 36 rats Were involved in the final analysis.Thirty days after operation, aortic tunica intima was thickened in the model group, mRNA expression of focal adhesion kinase was increased, and total protein and phosphorylated protein were higher in the model group than those in the control group;however,proliferation of tunica 5ntima vasorum was lightened in the treatment group, activity of mRNA expression of focal adhesion kinase was decreased, and total protein and phosphorylated protein were lower in the treatment group than those in the model group.CONCLUSION: Telmisartan can remarkably relieve proliferation of tunica intima after denudation and inhibit expression and activation of focal adhesion kinase after vascular injury.Effect of telmisartan on vascular-injured remodeling may be related to inhibiting expression and activation of focal adhesion kinase.