和厚朴酚对大鼠心肌缺血再灌注损伤的保护作用

The protective effects of Honokiol on myocardial ischemia-reperfusion injury in rats

目的研究和厚朴酚(Honokiol,HON)对大鼠急性心肌缺血再灌注损伤(I/R)的影响并初步探讨其可能机制。方法 SD大鼠分为3组。对照组假手术+腹腔注射HON 10^(-7)g/kg,I/R组缺血30 min再灌注120min,HON组I/R+腹腔注射HON 10^(-7)g/kg。观测各组大鼠左心室血流动力学、心电图(ECG)和血浆肌酸激酶(CK)的变化,分离成年大鼠心肌细胞,Ion Optix光谱荧光检测系统记录HON对钙瞬变的影响。结果 (1)与对照组比较,I/R组大鼠左心室收缩末压(LVSP)、左心室最大上升速率(+dp/dtmax)、左心室最大下降速率(-dp/dtmax)明显降低(P<0.05),左心室舒张末压(LVEDP)明显升高(P<0.05);心律失常的发生率和血浆肌酸激酶(CK)明显升高(P<0.05)。(2)与I/R组比较,HON组LVSP、+dp/dtmax、-dp/dtmax明显升高(P<0.05),LVEDP明显降低(P<0.05);同时,再灌注时出现心律失常时间明显延迟(P<0.05),再灌注后的前3 min内发生心律失常的时间总和和频率明显下降(P<0.05),室颤的发生率明显减少(P<0.05);血浆CK的活性显著降低(P<0.05)。(3)3μmol/L HON明显降低成年大鼠心肌细胞钙瞬变幅度。结论 HON能改善心肌I/R时心功能降低,并拮抗再灌早期出现的心律失常,机制可能与减少细胞内游离钙、减轻I/R时钙超载有关。

Objective To investigate the protective effects of honokiol on myocardial ischemia - reperfusion （ I/ R） injury in rats. Methods SD rats were assigned into CTL group, I/R model group and HON group. The hemodynamics data, ECG and the serum ereatine kinase （CK） were measured. Adult rat cardiomyoeytes were isolated with Langendorff perfuse system. Myocardial cell calcium transient was detected with IonOptix fluorescence spectrum detect system. Results Compared with CTL group, LVSP, ＋ dp/dtmax and - dp/dtmax were significantly lower while LVEDP significantly higher in I/R groups （P 〈 0. 05 ）. Compared with I/R group, LVSP, ＋ dp/dtmax and - dp/dtmax were significantly higher while LVEDP significantly lower in HON group （ P 〈 0. 05 ）. Compared with CTL group, the incidence of ar- rhythmias and activity of CK were significantly higher in I/R group （P 〈 0. 05 ）. Compared with I/R group, the incidence of arrhythmias and activity of CK were reduced （ P 〈 0. 05 ）. Meanwhile, during the first 3 minutes of reperfusion, the on- set time of arrhythmia was significantly prolonged （ P 〈 0. 05 ） , the duration and frequency of arrhythmia were reduced （ P 〈 0. 05 ） in HON group. HON reduced myocardial cell calcium transient amplitude. Conclusion HON could improve the cardiac function in myocardial I/R and reduced early reperfusion arrhythmia. This mechanism may be related to the reduction in intracellular Ca2 ＋ and calcium overload in myocardial I/R.