Effects Of Shikonin On IKur/hKv1.5 Current And Rat Models Of Paroxysmal Atrial Fibrillation

Background:Atrial fibrillation(Atrial fibrillation AF)is one of the most common arrhythmias in the clinic.Its complications such as thromboembolic events and heart failure are seriously life-threatening,and the prevalence is higher in the elderly.The process of aging is increasingly affecting the quality of life of the people,and has a higher mortality and disability rate.At present,the current treatment methods are mainly drug therapy and catheter ablation.Drug therapy often recurs and is accompanied by adverse reactions.Catheter ablation has been widely used in atrial fibrillation,but its treatment is invasive and costly.There are still shortfalls in the number of patients,so it is necessary to develop new antiarrhythmic drugs for AF.Objective:Explore the effect of shikonin on the atrial-specific expression of Ikur/hKvl.5 potassium ion channel current,and the prevention and treatment effect of shikonin on paroxysmal atrial fibrillation model rats;reveal the effects of shikonin on the prevention and treatment of atrial fibrillation Possible mechanism to provide new ideas for Chinese medicine treatment of AF.Methods:In vitro experiments:hKv1.5 potassium channel genes were transferred into CHO cell membranes for expression,shikonin was administered at different concentrations,and whole-cell patch clamp technology was used to record and observe changes in hKvl.5 potassium channel currents under different voltage conditions.In vivo experiments:An animal model of paroxysmal atrial fibrillation was established using ACh-CaCl2 mixed solution injected into the tail vein of rats.Forty SD rats were randomly divided into four groups:atrial fibrillation model group,shikonin treatment group,amiodarone-positive drug group,and normal control group,10 rats in each group.The blank group was not modeled.The remaining three groups were continuously injected with drugs in the tail vein for 7 days.The shikonin group and the amiodarone group were administered orally.After the experiment,aortic blood was separated from atrial tissue and placed in both electron microscopy solution and paraformaldehyde solution.HE staining and Masson staining were used to calculate the time and duration of atrial fibrillation induction in each group of ECG.The ELISA method was used to detect biochemical indicators.Results:1.Shikonin can inhibit the atrial-specific expression of Ikur/hKv1.5 potassium ion channel and can be used as an Ikur/hKv1.5 potassium channel blocker.2.Shikonin can reduce the sensitivity of rat induced atrial fibrillation and shorten Duration of atrial fibrillation;3.Shikonin can increase the atrial muscle cell cross-section of atrial fibrillation model and inhibit atrial expansion;4.Shikonin improves fibrosis and ultrastructure of atrial tissue;5.Shikonin Improves plasma levels of IL-6 and TNF-? in atrial fibrillation rats.