摘要
目的观察血管紧张素III(AT1)型受体阻断剂厄贝沙坦(irbesartan)预处理对大鼠心肌缺血再灌注性心律失常的保护作用,并探讨其可能机制。方法实验动物经厄贝沙坦预处理1周后,相对于对照组和手术组,应用体外心脏灌流方法在体外心脏上观察再灌注45min内室性心律失常的发生和悬浮微电极方法在体内心脏观察再灌注45min内动作电位的变化;同时我们检测心肌标本AT1受体及肌浆网钙ATP酶(sar coplasmicreticulum Ca2+-ATPase,SERCA) mRNA表达水平的变化。结果厄贝沙坦组在再灌注45min内平均室速、室颤事件明显减少(P<0.01),且在再灌注45min内动作电位改善明显;同时发现,相对于对照组,手术组心脏AT1 mRNA表达升高而SERCA mRNA表达下调,厄贝沙坦可逆转上述表达变化。结论厄贝沙坦具有晚期药理性预适应的抗再灌注性心律失常作用,其机制可能与动作电位的改善、阻断AT1的表达、逆转SERCA mRNA水平下降,从而减少细胞内钙超载有关。
OBJECTIVE To investigate the anti-arrhythmic effect of angiotensin II receptor blocker （ARBs） of irbesartan on reperfusion-induced arrhythmia in rat heart, and to explore its possible mechanisms. METHODS After the precondition of irbesartan for 1 week, Langendroff reperfusion and floating microelectrode were used to observe the incidence and duraion of reperfusion induced ventricular tachycardia （VT） and ventricular fibrillation（VF） in the period of 45 min reperfusion. Meanwhile, the mRNA levels of AT1 and sarcoplasmic reticulum （SR）CaZ＋ATPase （SERCA） was measured by reverse transcription-polymerase chain reaction（RT-PCR ）. RESULTS The average episodes of VT and VF were significantly reduced during reperfusion period in irbesartan group. Meanwhile, the levels of SERCA mRNA were lower while AT1 was increased in the ischichemial reperfusion（IR） isolated hearts group compared with those in the control group. Irbesartan reversed these changes in gene expression. CONCLUSION Angiotensin II receptor blockers（Irbesartan） pretreatment can offer antiarrhythmia effect on reperfusion-induced VT and VF, and the mechanisms may involved improving in action potential, upregulating the mRNA expression of SERCA by blocking the AT1 receptor.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2009年第20期1543-1546,共4页
Chinese Pharmaceutical Journal
关键词
心肌再灌注损伤
心律失常
厄贝沙坦
预处理
myocardial reperfusion injury
arrhythmia
irbesartan
precondition
