安息香调节ACE/AngⅡ/AT1R轴改善心肌梗死模型大鼠的机制研究  

Mechanism of Benzoin regulating ACE/AngⅡ/AT1R axis to improve myocardial infarction model rats

作　　者：王立映 王佳俊 王建[1] 付尹 杨显娟 李金秀 徐卓 龚道银[2] WANG Li-ying;WANG Jia-jun;WANG Jian;FU Yin;YANG Xian-juan;LI Jin-xiu;XU Zhuo;GONG Dao-yin(Chengdu University of Traditional Chinese Medicine,Chengdu 611137,Sichuan;The Affiliated Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610072,Sichuan)

机构地区：[1]成都中医药大学,四川成都611137 [2]成都中医药大学附属医院,四川成都610072

出　　处：《中药与临床》2023年第6期43-50,54,共9页Pharmacy and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金(81873023)。

摘　　要：目的:探讨安息香改善急性心肌梗死(AMI)及调节肾素-血管紧张素(Ras)的可能机制。方法:SD雄性成年大鼠,按体重随机分为假手术组,模型组,溶剂模型组,硝酸甘油组、安息香1.0、0.5、0.25 g·kg^(-1)共7组,每组16只。采用冠状动脉左前降支(LAD)结扎法建立心肌梗死模型;于预给药1次后及治疗给药第7 d,采集心电ST段、QT间期、QRS时限、Q波、左室舒张压(LVDP)、左室舒张期末压(LVEDP)、左室内压上升最大速度(+dp/dtmax)、左室心肌收缩成分实测最大缩短速度(fpm);试剂盒微板法检测给药第7 d后血清天门冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH),酶联免疫法(ELISA)测肌酸激酶同工酶(CK-MB)活性、血管紧张素转化酶(ACE)、血管紧张素转化酶2(ACE2)、血管紧张素Ⅱ(AngⅡ)、血管紧张素1~7(Ang1~7),心肌组织醛固酮(ALD)含量;计算心脏指数,TTC染色法计算心肌梗死率;RT-PCR法测ACE、ACE2、AngⅡ、血管紧张素Ⅱ1型受体(AT1R)、Mas受体(MasR)mRNA表达情况;免疫组织化学法检测AT1R、TGF-β_(1)、Collagen-Ⅰ蛋白表达水平。结果:假手术组比较,模型组大鼠ST段、QT间期、QRS时限、Q波,心肌力学LVDP、LVEDP,酶学指标AST、LDH、CK-MB,血清ACE、AngⅡ、组织ALD,心脏系数及梗死率均显著升高,梗死区ACE、AngⅡ、AT1R的mRNA表达量及AT1R、TGF-β_(1)、Collagen-Ⅰ蛋白表达量显著增加;+dp/dtmax及fpm显著降低(P<0.05,P<0.01)。安息香3个剂量均能显著抑制模型大鼠ST段抬高、缩短QRS时限、降低Q波波幅和LVEDP,抑制血清酶AST、降低血清ACE;安息香1.0、0.5 g·kg^(-1)组还能显著降低CK-MB、降低梗死率及心脏系数,降低AngⅡ在血清和梗死区组织的mRNA表达量,降低组织ALD含量;下调心肌组织AT1R的mRNA和蛋白表达,降低TGF-β_(1)、Collagen-Ⅰ蛋白的表达量;显著增大左室+dp/dtmax、增加血清ACE2、Ang1~7含量。其中安息香1.0 g·kg^(-1)组显著降低LVDP、血清LDH、组织ACE的mRNA表达Objective:To investigate the possible mechanism of Anxixiang ameliorating acute myocardial infarction(AMI)and regulating renin-angiotensin(Ras).Method:SD male adult rats were randomly divided into 7 groups according to body weight:sham operation group,model group,solvent model group,nitroglycerin group,Anxixiang 1.0,0.5,0.25 g·kg^(-1),with 16rats in each group.Myocardial infarction model was established by ligation of the left anterior descending coronary artery(LAD).ST segment,QT interval,QRS duration,Q wave,left ventricular diastolic blood pressure(LVDP),left ventricular end-diastolic blood pressure(LVEDP),maximum rate of left ventricular pressure rise(+dp/dtmax),and measured maximum rate of reduction(fpm)of left ventricular myocardial systolic components were collected after one time of preadministration and on the 7th day of treatment administration.Serum aspartate aminotransferase(AST)and lactate dehydrogenase(LDH)were detected 7days after administration by microplate assay.Creatine kinase isoenzyme(CK-MB)activity,angiotensin converting enzyme(ACE),angiotensin converting enzyme 2(ACE2),angiotensinⅡ(AngⅡ),angiotensin 1-7(ANG1-7),and aldosterone(ALD)content in myocardial tissue were measured by enzyme-linked immunoassay(ELISA).The heart index was calculated and the rate of myocardial infarction was calculated by TTC staining.mRNA expressions of ACE,ACE2,AngⅡ,angiotensin Ⅱ1 receptor(AT1R)and Mas receptor(MasR)were measured by RT-PCR.The protein expression levels of AT1R,TGF-β_(1) and Collagen-Ⅰwere detected by immunohistochemistry.Result:Compared with sham operation group,ST segment,QT interval,QRS duration,Q wave,myocardial mechanical LVDP,LVEDP,enzyme index AST,LDH,CK-MB,serum ACE,AngⅡ,tissue ALD,and heart coefficient and infarction rate were signiffcantly increased in model group.mRNA expression levels of ACE,AngⅡ and AT1R and protein expression levels of AT1R,TGF-β_1 and CollagenⅠwere signiffcantly increased in infarction area.+dp/dtmax and fpm were signiffcantly decreased(P<0.05,P<0.01).

关 键 词：安息香 心肌梗死 心电生理 心肌力学 RAS系统 

分 类 号：R285.5[医药卫生—中药学]