Page 40 - 2021年18期

ABSTRACT OBJECTIVE：To study the effects of dexmedetomidine on ventricular arrhythmia in myocardial hypertrophy model
rabbits and the expression of calcium ion/calmodulin-dependent protein kinase Ⅱ （CaMK Ⅱ） in myocardial tissue of rabbits.
METHODS： The rabbits were randomly divided into sham operation group， model group， dexmedetomidine low-dose，
medium-dose and high-dose groups （10， 25， 50 μ g/kg）， CaMK Ⅱ inhibitor KN-93 group （10 mg/kg）， high-dose of
dexmedetomidine+KN-93 group（50 μg/kg+10 mg/kg），with 10 rabbits in each group. Except for the sham operation group，other
groups received abdominal aortic coarctation to induce myocardial hypertrophy model. After surgery，administration groups were
given relevant dose of dexmedetomidine or/and intraperitoneal injection of KN-93；sham operation group and model group were
given constant volume of normal saline intravenously，once every other day，for consecutive 8 weeks. After last medication，
programmed stimulation was used to induce ventricular arrhythmia. The induction rate of early posterior depolarization（EAD）and
tip torsion type ventricular tachycardia（Tdp）were recorded. Left ventricular ejection fraction（LVEF）and left ventricular shortener
fraction（FS）were measured. QT interval，transventricular wall repolarization dispersion（TDR）and transmembrane 90％ action
potential duration（APD90）of endocardial and epicardial cardiomyocytes in wedge-shaped myocardium were recorded. The ratio of
heart weight to body weight （HW/BW） and the thickness of left ventricular wall （LVT） were measured and calculated. The
cross-sectional area of cardiomyocytes，mRNA expression of ANP and BNP as well as protein expression of CaMKⅡ and p-CaMKⅡ
in myocardial tissue was measured. RESULTS：Compared with sham operation group，the induction rate of EAD and Tdp，HW/BM，
LVT，mRNA expression of ANP and BNP and protein relative expression of CaMKⅡ and p-CaMKⅡ in cardiac tissue were all
increased significantly，while LVEF and FS were decreased significantly；QT interval，APD90 of endocardial and epicardial
cardiomyocytes were all prolonged significantly；TDR was increased significantly，while cross-sectional area of cardiomyocytes
was increased significantly in model group（P＜0.05）. Compared with model group，induction rate of EAD and Tdp，HW/BW
（except for dexmedetomidine low-dose group），LVT（except for dexmedetomidine low-dose group），mRNA relative expression of
ANP（except for dexmedetomidine low-dose group）and BNP（except for dexmedetomidine low-dose group）as well as protein
relative expression of CaMK Ⅱ and p-CaMK Ⅱ were all decreased significantly in administration groups；the levels of LVEF
（except for dexmedetomidine low-dose group） and FS （except for dexmedetomidine low-dose group） were all increased
significantly； QT interval， APD90 of endocardial and epicardial cardiomyocytes were shortened significantly； TDR and
cross-sectional area of cardiomyocytes（except for dexmedetomidine low-dose group）were decreased significantly（P＜0.05）；the
improvement effects of dexmedetomidine high-dose group were significantly better than those of dexmedetomidine low-dose and
medium-dose groups（P＜0.05）. Compared with dexmedetomidine high-dose group and KN-93 group，the improvement of above
indexes were all more significant in high-dose of dexmedetomidine+KN-93 group（P＜0.05）. CONCLUSIONS：Dexmedetomidine
can reduce the induction rate of ventricular arrhythmia and improve myocardial hypertrophy in myocardial hypertrophy model
rabbits，the mechanism of which may be associated with down-regulation of CaMKⅡ expression.
KEYWORDS Dexmedetomidine；Myocardial hypertrophy；Ventricular arrhythmia；CaMKⅡ；Rabbit

心肌肥厚是心肌梗死、心律失常等一系列心血管疾 早期后除极（EAD）和尖端扭转型室性心动过速（Tdp）的
病的病理基础，主要表现为心肌间质增生和心室肌肥 诱发率，检测左室射血分数（LVEF）和左心室缩短分数
厚 。其中，心室肌肥厚随病情的进展容易诱发恶性心 （FS），同步记录家兔离体楔形心肌组织QT间期、跨室壁
[1]
律失常，甚至诱发急性心肌梗死、猝死，严重影响患者的 复极离散度（TDR）和内、外膜心肌细胞跨膜动作电位复
[2]
生命健康 。研究表明，肥厚心肌的心律失常与钙调蛋 极90％时程（APD90），评价右美托咪定的抗心律失常作
[3]
白的激活密切相关 。钙离子-钙调蛋白依赖性蛋白激 用；同时，检测右美托咪定对家兔心肌细胞横截面积以
酶Ⅱ（CaMKⅡ）的活性在肥厚心肌组织中显著增强，并 及心肌组织中心房钠尿肽（ANP）、脑钠肽（BNP）mRNA
可通过作用于 L 型钙离子通道（LTCC），致使心肌细胞 和CaMKⅡ、磷酸化CaMKⅡ（p-CaMKⅡ）蛋白表达的影
钙离子（Ca ）超载，进而提高肥胖和高血脂患者恶性心 响，为右美托咪定用于改善心肌肥厚致心律失常提供科
2+
[4]
律失常的发生率 。有研究报道，右美托咪定可以通过 学依据。
减弱LTCC电流来影响心肌肥厚和充血性心力衰竭患者 1 材料
的心肌收缩力和心脏电活动，这一作用可能与其缓解心 1.1 主要仪器
2+
[5]
肌细胞的 Ca 超负荷相关 。多项临床研究证明，右美 本研究所用主要仪器有：PowerPac 型基础电泳仪、
托咪定可降低心脏病患者术后异位心动过速和快速心 Mini-protean型垂直板电泳槽、Trans-blot型电转膜系统、
律失常的发生率 [6－8] 。基于此，本研究以心肌肥厚模型 T100 型聚合酶链式反应（PCR）仪（美国 Bio-Rad 公司），
家兔为对象，以程序性刺激诱发室性心律失常，记录其 YC-2 型程控刺激器、RM6240B 型多道生理信号采集处

·2210 · China Pharmacy 2021 Vol. 32 No. 18 中国药房 2021年第32卷第18期