摘要
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.④Western blot检测AMPA受体亚基(GRIAl)、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.
Abstract
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 frequen-cy of central entries,the cumulative time in the center,and the number of rearing by open field test and AF induc-ibility 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 ex-pression 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 de-creased,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 myocar-dial apoptosis were increased significantly;the expres-sion of GRIA1,Caspase-3,Cleaved caspase-3 and Bax was increased and the expression of Bcl-2,p-PI3K/PI3K and p-AKT/AKT was decreased in ADN+LY group.Conclusion The inhibition of AMPA receptors can im-prove myocardial cell apoptosis and reduce the inducibility of atrial fibrillation through PI3K/AKT pathway in anxiety rats.[Chinese Journal of Cardiac Pacing and Electro-physiology,2024,38(3):180-186]
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