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Antiarrhythmic effect of atorvastatin on autoimmune myocarditis is mediatedby improving myocardial repolarization

机译:阿托伐他汀对自身免疫性心肌炎的抗心律失常作用是通过改善心肌复极化来介导的

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3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins, are known to inhibit cholesterol biosynthesis and prevent inflammation and oxidative stress. To explore the effects of atorvastatin on inflammatory progression and major cardiac electrophysiological changes in myocarditis, we used an animal model of experimental autoimmune myocarditis (EAM). In this model, BALB/c mice were treated with atorvastatin and we evaluated the levels of inflammation markers and currents of ionic channels that contribute to the duration of action potential (APD) of ventricular myocytes. We demonstrated that atorvastatin treatment attenuated inflammatory infiltration and suppressed the increase in TNF-a and IFN--y levels in EAM mouse hearts. In the whole-cell patch-clamp experiment, ventricular cardiomyocyte APD was prolonged in EAM group, and atorvastatin blocked this change. We further found that atorvastatin attenuated the significant decrease hi outward potassium currents in EAM myocytes. Our results suggested that atorvastatin may ameliorate EAM progression by reducing inflammatory cytokine level. Atorvastatin exerted the antiarrhythmic effects by selectively affecting cardiomyocyte ion channel activity and therefore improves myocardial repolarization.
机译:3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂或他汀类药物可抑制胆固醇的生物合成并防止炎症和氧化应激。为了探索阿托伐他汀对心肌炎的炎症进展和主要心脏电生理变化的影响,我们使用了实验性自身免疫性心肌炎(EAM)的动物模型。在该模型中,用阿托伐他汀治疗BALB / c小鼠,我们评估了炎症标记物的水平和离子通道的电流,这些离子通道对心室肌细胞的动作电位(APD)持续时间有贡献。我们证明了阿托伐他汀治疗可减弱EAM小鼠心脏中的炎症浸润并抑制TNF-a和IFN-γ水平的增加。在全细胞膜片钳实验中,EAM组的心室心肌细胞APD延长,阿托伐他汀阻止了这一变化。我们进一步发现,阿托伐他汀减弱了EAM心肌细胞中向外钾电流的显着降低。我们的结果表明,阿托伐他汀可以通过降低炎症细胞因子水平来改善EAM进展。阿托伐他汀通过选择性影响心肌细胞离子通道活性发挥抗心律失常作用,因此改善了心肌复极化。

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