AMPA受体对焦虑障碍大鼠心房颤动易感性的影响

The effect of AMPA receptors on the susceptibility to atrial fibrillation in anxious rats

目的探讨AMPA受体对焦虑障碍大鼠心房颤动(简称房颤)易感性的影响。方法采用6~8周雄性SD大鼠48只,随机分为对照组(CTL组)、模型组(AD组)、模型+AMPA受体拮抗剂(NBQX)组(ADN组)和ADN+PI3K抑制剂(LY294002)组(ADN+LY组)。以空瓶饮水刺激方法制备焦虑障碍大鼠模型。21天空瓶饮水刺激结束后,对各组大鼠进行:(1)旷场实验检测焦虑样行为相关指标:进入中心场次数、在中心场次的时间和抬爪次数。(2)电生理检查观察大鼠房颤诱发率。(3)取左心房组织,进行细胞凋亡检测。(4)Western blot检测AMPA受体亚基(GRIA1)、Caspase-3、Cleaved capase-3、Bax、Bcl-2、PI3K、p-PI3K、AKT以及p-AKT在心肌组织中的表达情况。结果与CTL组相比,AD组大鼠焦虑行为相关指标降低,房颤诱发率增加,心肌凋亡显著增加,GRIA1、Caspase-3、Cleaved caspase-3以及Bax蛋白表达升高,Bcl-2蛋白表达及p-PI3K/PI3K、p-AKT/AKT降低;与AD组相比,ADN组大鼠房颤诱发率降低,细胞凋亡减少,心房组织中GRIA1、Caspase-3、Cleaved caspase-3以及Bax蛋白表达降低,Bcl-2、p-PI3K/PI3K和p-AKT/AKT升高;与ADN组大鼠相比,ADN+LY组大鼠房颤诱发率增加,心肌凋亡显著增加,GRIA1、Caspase-3、Cleaved caspase-3以及Bax蛋白表达升高,Bcl-2、p-PI3K/PI3K和p-AKT/AKT降低。结论抑制AMPA受体可通过PI3K/AKT通路改善焦虑障碍大鼠心肌细胞凋亡,降低房颤诱发率。

Objective To explore the effect of AMPA receptors on the susceptibility to atrial fibrillation(AF)in anxiety rats.Methods Sprague-Dawley(SD)rats of 6-8 weeks were used to establish anxiety rat model by empty bottle stimulation.Rats were randomly divided into control group(CTL group),model group(AD group),AMPA receptor antagonist(NBQX)group(ADN group)and ADN+PI3K inhibitor(LY294002)group(ADN+LY group).After the 21-day stimulation of empty bottle stimulation,the rats in each group were examined the frequency of central entries,the cumulative time in the center,and the number of rearing by open field test and AF inducibility by electrophysiological test.The left atrial tissue was taken for apoptosis detection.The expression of GRIA1,Caspase-3,Cleaved caspase-3,Bax,Bcl-2,PI3K,p-PI3K,AKT and p-AKT in myocardial tissue was detected by Western blot.Results Compared with CTL group,the expression of anxiety behavior related indexes in AD group decreased;the induction rate of AF was increased,myocardial apoptosis was increased significantly,the expression of GRIA1,Caspase-3,Cleaved caspase-3 and Bax were increased,while the expression of Bcl-2,p-PI3K/PI3K and p-AKT/AKT was decreased.Compared with AD group,the induction rate of AF and apoptosis in ADN group were decreased,the expression of GRIA1,Caspase-3,Cleaved caspase-3 and Bax in atrial tissue were decreased,while the expression of Bcl-2,p-PI3K/PI3K and p-AKT/AKT was increased in ADN group.Compared with ADN group,theinduction rate of AF and myocardial apoptosis were increased significantly;the expression of GRIA1,Caspase-3,Cleaved caspase-3and Bax was increased and the expression of Bcl-2,p-PI3K/PI3Kand p-AKT/AKT was decreased in ADN+LY group.Conclusion The inhibition of AMPA receptors can improve myocardial cell apoptosis and reduce the inducibility of atrial fibrillation through PI3K/AKT pathway in anxiety rats.