CAJ | 학술논문

目的评价心肌钙调素依赖性蛋白激酶Ⅱ(CaMKⅡ)与左西孟旦抗心肌缺血再灌注致大鼠心律失常作用的关系.方法健康成年雄性Wistar大鼠30只,体重250 ～ 300 g,采用随机数字表法,将其分为3组(n=10):对照组(C组)、缺血再灌注组(I/R组)和左西孟旦组(L组).采用Langendorff灌注装置建立离体心脏灌注模型.平衡灌注20 min后,C组用K-H液继续灌注60 min; I/R组缺血30 min后,K-H液灌注30 min;L组缺血30 min后,用含左西孟旦300 nmol/L的K-H液灌注30min.分别于缺血前即刻、再灌注15和30 min时记录左心室发展压(LVDP)、左心室舒张末压(LVEDP)、左心室内压最大上升速率(+dp/dtmax)、左心室内压最大下降速率(-dp/dtmax)和心率(HR).记录再灌注期间心律失常的发生情况,并进行评分.于再灌注30 min时取心尖部组织,测定细胞内钙离子浓度([Ca2+]i),取左心室心肌组织,测定CaMKⅡ的活性.结果与C组比较,I/R组心律失常评分、[Ca2+]i和CaMKⅡ活性升高,再灌注15和30 min时LVDP、+dp/dtmax、-dp/dtm1ax和HR降低,LVEDP升高(P＜0.05);与I/R组比较,L组室性早搏数量、心律失常评分、[Ca2+]i和CaMKⅡ活性降低,再灌注15和30 min时LVDP、+dp/dtmax、-dp/dtmax和HR升高,LVEDP降低(P＜0.05).结论左西孟旦降低心肌缺血再灌注致大鼠心律失常的机制与抑制CaMKⅡ活性有关.
목적 평개심기개조소의뢰성단백격매Ⅱ(CaMKⅡ)여좌서맹단항심기결혈재관주치대서심률실상작용적관계.방법 건강성년웅성Wistar대서30지,체중250 ～ 300 g,채용수궤수자표법,장기분위3조(n=10):대조조(C조)、결혈재관주조(I/R조)화좌서맹단조(L조).채용Langendorff관주장치건립리체심장관주모형.평형관주20 min후,C조용K-H액계속관주60 min; I/R조결혈30 min후,K-H액관주30 min;L조결혈30 min후,용함좌서맹단300 nmol/L적K-H액관주30min.분별우결혈전즉각、재관주15화30 min시기록좌심실발전압(LVDP)、좌심실서장말압(LVEDP)、좌심실내압최대상승속솔(+dp/dtmax)、좌심실내압최대하강속솔(-dp/dtmax)화심솔(HR).기록재관주기간심률실상적발생정황,병진행평분.우재관주30 min시취심첨부조직,측정세포내개리자농도([Ca2+]i),취좌심실심기조직,측정CaMKⅡ적활성.결과 여C조비교,I/R조심률실상평분、[Ca2+]i화CaMKⅡ활성승고,재관주15화30 min시LVDP、+dp/dtmax、-dp/dtm1ax화HR강저,LVEDP승고(P＜0.05);여I/R조비교,L조실성조박수량、심률실상평분、[Ca2+]i화CaMKⅡ활성강저,재관주15화30 min시LVDP、+dp/dtmax、-dp/dtmax화HR승고,LVEDP강저(P＜0.05).결론 좌서맹단강저심기결혈재관주치대서심률실상적궤제여억제CaMKⅡ활성유관.
Objective To evaluate the relationship between calmodulin protein kinase Ⅱ (CaMK Ⅱ) and levosimendan against arrhythmias induced by myocardial ischemia-reperfusion (I/R) in rats in vitro.Methods Thirty male Wistar rats,weighing 250-300 g,were randomly divided into 3 groups (n =10 each) using a random number table:control group (group C),I/R group and levosimendan group (group L).Their hearts were rapidly excised and perfused in a langendorff apparatus with K-H solution saturated with 95％ O2-5％ CO2 at 36.5-37.5 ℃.At 20 min of equilibration,the hearts were perfused with K-H solution for 60 min in group C.The hearts were subjected to 30 min of ischemia followed by 30 min reperfusion with K-H solution in group I/R.The hearts were subjected to 30 min of ischemia followed by 30 min reperfusion with K-H solution containing 300 nmol/L levosimendan in group L.Left ventricle developed pressure (LVDP),left ventricle end-diastolic pressure (LVEDP),+ dP/dt-dP/dtmax and heart rate (HR) were recorded immediately before ischemia and at 15 and 30 min of reperfusion.Arrhythmia was recorded during reperfusion and scored.Specimens were obtained from the apex of heart at 30 min of reperfusion for determination of the intracellular calcium concentration ([Ca2 +] i).Myocardial specimens were obtained from the left ventricle at 30 min of reperfusion to detect CaMK Ⅱ activity.Results Compared with group C,arrhythmia score,[Ca2+]i and CaMK [Ⅱ activity were significantly increased,and LVDP,+ dP/dtmax,-dP/dtmax and HR were decreased,and LVEDP was increased at 15 and 30 min of reperfusion in group I/R.Compared with group I/R,the number of ventricular premature beat,arrhythmia score,[Ca2+] i and CaMK Ⅱ activity were significantly decreased,and LVDP,+ dP/dtmax,-dP/dtmax and HR were increased,and LVEDP was decreased at 15 and 30 min of reperfusion in group L.Conclusion Inhibition of CaMK Ⅱ activity is involved in the mechanism by which levosimendan decreases the development of arrhythmias induced by myocardial I/R in rats.