急性心肌梗死大鼠血管紧张素Ⅱ对PAI-1和tPA表达的作用及其机制  

Effects of angiotensin Ⅱ on expressions of PAI-1 and tPA in rats with acute myocardial infarction

作　　者：黄妍[1] 李法琦[1] 李万玉[2] 周平[1] 周希[3] 赵玉伟[1] 邱炯[1] 

机构地区：[1]重庆医科大学附属第一医院老年病科心血管病组,重庆400016 [2]重庆医科大学药学院药物分析教研室,重庆400016 [3]重庆市急救医疗中心重庆市第四人民医院心内科,重庆400015

出　　处：《吉林大学学报（医学版）》2011年第1期41-46,I0001,共7页Journal of Jilin University：Medicine Edition

基　　金：重庆市卫生局医学科研项目资助课题(03-2-121)

摘　　要：目的:探讨急性心肌梗死(AMI)大鼠血管紧张素Ⅱ(AngⅡ)经AngⅡ1型受体(AT1R)激活细胞外信号调节激酶(ERK)对纤溶酶原激活物抑制剂-1(PAI-1)和组织型纤溶酶原激活物(tPA)活性的调节作用。方法:24只健康SD大鼠,按随机数字表法随机分为假手术组(n=8)、AMI组(n=8)和特异性ERK上游激酶抑制剂(PD98059)组(n=8),用结扎左冠状动脉前降支方法制作大鼠AMI模型,建模后14d,制备心肌组织切片观察心肌组织病理学改变;放射免疫法检测大鼠血浆和主动脉组织匀浆AngⅡ含量;发色底物法检测血浆和主动脉孵育液PAI-1和tPA活性;Western blotting分析法检测主动脉组织匀浆磷酸化ERK1/2(p-ERK1/2)和ATlR蛋白表达水平。结果:①假手术组心肌纤维排列整齐,核规则;AMI组心肌纤维消失中断,部分心肌细胞空泡变,部分心肌纤维及核溶解消失,肌纤维呈空管状,梗死区为大量纤维结缔组织取代并有炎症细胞浸润;PD98059组AMI的病理改变明显减轻。②与假手术组比较,AMI组血浆和主动脉组织匀浆AngⅡ含量及血浆和主动脉孵育液PAI-1活性均显著增高(P<0.05),但血浆和主动脉孵育液tPA活性及其tPA/PAI-1比值均明显降低(P<0.05)。③与假手术组比较,AMI组主动脉组织匀浆p-ERK1/2和ATlR蛋白表达水平均显著增高(P<0.05或P<0.01)。④各组大鼠血浆和主动脉组织匀浆AngⅡ含量、血浆和主动脉孵育液PAI-1活性及主动脉组织匀浆p-ERK1/2和ATlR蛋白表达水平之间呈正相关关系(r=0.85～0.94,P<0.01)。⑤与AMI组比较,PD98059组血浆和主动脉组织匀浆AngⅡ含量、血浆和主动脉孵育液PAI-1活性、主动脉组织匀浆p-ERK1/2和ATlR蛋白表达均显著降低(P<0.05),但血浆和主动脉孵育液tPA活性及其tPA/PAI-1比值均明显增高(P<0.05)。结论:AMI时AngⅡ具有诱导PAI-1但抑制tPA合成与分泌的作用,其机制可能与AngⅡ经AT1R激活ERK有关。Objective To explore the effects of angiotensin Ⅱ（AngⅡ）on the synthesis and release of plasminogen activator inhibitor 1（PAI-1） and tissue plasminogen activator（tPA） through modulating extracellular signal regulated kinase（ERK） activated with AngⅡtype 1 receptor（ATlR） in rats with acute myocardial infarction（AMI）.Methods 24 Sprague-Dawley rats were randomly divided into 3 groups：sham operation group（n=8）,AMI group（n=8）,and PD98059 group（n=8）.The rat model of AMI was established by ligating left anterior descend coronary artery.On the 14th day after AMI,the tissue slices of myocardium were prepared and the histopathological changes of myocardium were observed with microscope;the AngⅡ levels in plasma and aortic tissue were measured by radioimmunoassay;the PAI-1 and tPA activities were measured by spectrophotometric assay;the expressions of p-ERK1/2 and ATlR proteins in the homogenized aortic tissue were examined by Western blotting in rats in various groups.Results ①The HE-dyed tissue slices of myocardium showed that the myocardium was normal（cardiac muscle fibers to line up in order and nucleus being rule） in sham operation group but abnormal（the disruption,cavity and dissolution of cardiac muscle fibers,the lysis of nucleus,the proliferation of fibrous connective tissue and the infiltration of inflammatory cells） in AMI group,and the damaged myocardium after AMI was remarkably improved in PD98059 group.② Compared with sham operation group,the AngⅡlevels and PAI-1 activities in plasma and incubation solution for aorta were significantly increased（all P0.05）,but the activity of tPA and the ratio of tPA to PAI-1 in plasma and incubation solution for aorta were decreased remarkably in AMI group（all P0.05）.③Compared with sham operation group,the expressions of p-ERK1/2 and ATlR proteins in homogenized aortic tissue were significantly increased（all P0.05）.④The plasma AngⅡ level and PAI-1 activity,aortic AngⅡ level and PAI-1 activity were a

关 键 词：心肌梗死 细胞外信号调节激酶 血管紧张素Ⅱ 纤溶酶原激活物抑制剂-1 组织型纤溶酶原激活物 大鼠 Sprague-Dawley 

分 类 号：R541.4[医药卫生—心血管疾病]