加巴喷丁通过PI3K-AKT信号通路减轻大鼠心肌缺血—再灌注损伤
Gabapentin alleviates myocardial ischemia-reperfusion injury through the PI3K-AKT signaling pathway
目的:观察加巴喷丁对心肌缺血-再灌注损伤的影响,并进一步探讨其机制。方法:清洁级雄性SD大鼠60只,10周龄,体重250 g~300 g,采用随机数字表法分为5组,每组12只:假手术组(Sham组)、心肌缺血-再灌注组(I/R组)、加巴喷丁组(Gap组)、LY294002组(LY组)和加巴喷丁+LY294002组(Gap+LY组)。采用左冠状动脉前降支结扎30 min和再灌注120 min,制备心肌缺血-再灌注损伤模型。记录心肌缺血前基线(T 0)、缺血30 min(T 1)和再灌注120 min(T 2)时大鼠的心率(Heart rate,HR)、平均动脉压(mean arterial pressure,MAP)和心率血压乘积(Rate pressure product,RPP),评价心肌缺血再灌注期间血流动力学变化;记录室性早搏(Premature ventricular complexes,PVCs)和室速/室颤(ventricular tachycardia/ventricular fibrillation, VT/VF)次数,评价缺血-再灌注期间心律失常。术毕取心肌组织采用2,3,5-氯化三苯基四氮唑(2,3,5-Triphenyltetrazoliumchloride,TTC)染色法,检测心肌梗死面积;免疫印迹法检测心肌组织PI3K和p-AKT蛋白表达水平。 结果:与I/R组相比,Gap组心肌梗死面积显著下降,PVCs和VT/VF次数显著减少,PI3K蛋白表达水平和p-AKT/AKT比值显著升高( P<0.05)。与Gap组相比,Gap+LY组心肌梗死面积显著增加,PVCs和VT/VF次数显著升高,PI3K蛋白表达水平和p-AKT/AKT比值显著降低( P<0.05)。 结论:加巴喷丁可以减轻心肌缺血再灌注损伤,与激活PI3K-AKT信号通路有关。
更多Objective:To evaluate the effect of gabapentin on myocardial ischemia-reperfusion injury and its mechanism.Methods:Sixty male clean SD rats, aged 10 weeks and weighing 250 g~300 g, were divided into 5 groups ( n=12) with 12 rats in each group by random number table method: Sham group, myocardial ischemia reperfusion group (group I/R), gabapentin group (group Gap), LY294002 group (group LY) and gabapentin +LY294002 group (group Gap +LY). The model of myocardial ischemia reperfusion injury was established by ligation of the left anterior descending coronary artery for 30 min and reperfusion for 120 min. Heart rate (HR), mean arterial pressure (MAP) and the rate pressure product (RPP) were recorded at baseline before ischemia (T 0) for 30 min (T 1) and reperfusion for 120 min (T 2) to evaluate hemodynamic changes during ischemia and reperfusion; The frequency of PVCs and VT/VF were recorded to evaluate the occurrence of arrhythmias during ischemia/reperfusion. TTC staining was used to detect myocardial infarction area. And the protein expression levels of PI3K and Akt in myocardial tissue were detected by Western blotting. Results:Compared with group I/R, the myocardial infarction area, PVCs and VT/VF times, and the protein expression levels of PI3K and p-Akt were significantly increased in group Gap ( P<0.05). Compared with group Gap, the area of myocardial infarction, the number of PVCs and VT/VF, and the protein expression of PI3K and p-Akt were significantly decreased in the group Gap +LY ( P<0.05). Conclusions:Gabapentin can alleviate myocardial ischemia-reperfusion injury, and its mechanism is related to the activation of PI3K-AKT signaling pathway.
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