抑糜酶素对急性心肌缺血大鼠室性心律失常的影响  

Effects of chymostatin on ventricular arrhythmias in rat with myocardial ischemia reperfusion in vivo

作　　者：赵眷梅 孙义润 龚天奎 王德国[1] 陈月云[1] 王安才[1] 

机构地区：[1]皖南医学院附属弋矶山医院老年医学科,安徽 芜湖241001

出　　处：《中国急救医学》2015年第10期934-938,I0003,共6页Chinese Journal of Critical Care Medicine

基　　金：国家自然基金（81200142）;安徽省自然科学基金（1208085QH156、1208085MH129）;皖南医学院附属弋矶山医院人才引进科研基金（YR201001）

摘　　要：目的：探讨抑糜酶素（ chymostatin ）对急性心肌缺血－再灌注室性心律失常的影响。方法 SD大鼠冠状动脉前降支结扎20 min后再灌注20 min，于建模前30 min腹腔注射抑糜酶素或生理盐水。采集心电图和心外膜电位图测定心率、90％单相动作电位复极时程（90％repolarization of action potential duration ， APD90）、动作电位离散度（APD dispersion， APDd），以积分法分析室性心律失常。放射免疫化学测定血管紧张肽Ⅱ（ angiotensinⅡ，AngⅡ），生物化学测定血管紧张肽Ⅰ转化酶（ angiotensin converting enzyme ， ACE）和糜酶活性。组织免疫荧光观察糜酶在心肌组织中表达。结果心肌缺血引起室性心律失常，APD90缩短及APDd增加，抑糜酶素降低室性心律失常积分，减轻缺血引起的APD90缩短及APDd扩大（P＜0．05）；心肌缺血时心肌组织局部糜酶和ACE活性，血浆和组织AngⅡ水平明显升高，抑糜酶素抑制组织糜酶活性并降低心肌组织AngⅡ（P＜0．05），对ACE活性、血浆AngⅡ水平无明显影响（P＞0．05）。结论抑糜酶素具有改善APD离散度及抗缺血性室性心律失常作用，其机制可能与抑制缺血心肌组织局部糜酶依赖性AngⅡ生成有关。Objective To investigate the effects of chymostatin （ a chymse inhibitor ） on the susceptibility of rat to ventricular arrhythmias （ VA） in an ischemia reperfusion （ IR） model in addition to attenuate myocardial injury .Methods Rats were subjected to left coronary artery occlusion for 20 min followed by 20 min reperfusion and received pretreatment with saline （ IR group ） or chymostatin （Chymostatin group） intraperitoneally 30min before ischemia.Elecrocardiogram and monophasic action potentials were recorded and analyzed for heart rate , 90% repolarization of action potential duration （ APD90 ） and APD dispersion （ APDd ） .A VA score system was used to test susceptibility of VA . Renin, angiotensinⅡ（ AngⅡ）, angiotensin converting enzyme （ ACE） and chymase activities were assayed.Chymase expression in myocardial tissue was determined by immunofluorescence staining . Results Myocardial ischemia resulted in VA , APD90 shortening and APDd enlargement .Pretreatment with chymostatin could reduce VA score , APD90 shortening and APDd enlargement （ P 〈0.05 ）. Chymostatin pretreatment significantly reduced AngⅡlevel and chymase activity in ischemic myocardial tissue （ P 〈0.05 ） without altering ACE activity and plasma Ang Ⅱ level （ P 〈0.05 ）. Immunofluorescence staining also revealed chymase increased in myocardial tissue of IR group and partly attenuated of chymostatin group . Conclusion The present study demonstrated that Chymostatin ameliorated APD dispersion and ischemic VAs , and its mechanism may be correlated with chymse -dependent AngⅡproduction .

关 键 词：心肌缺血-再灌注 室性心律失常 单相动作电位 糜酶 抑糜酶素 血管紧张肽Ⅱ 血管紧张肽转换酶 

分 类 号：R541.7[医药卫生—心血管疾病]