Lithium chloride maintains the gap junction of hypoxic myocardium by inhibiting glycogen synthase kinase 3β / 重庆医学

ABSTRACT

Objective To study the effect of lithium chloride on the gap junction in the myocardium under chronic hypoxia.Methods Twenty-five C57BL/6J mice were randomly divided into normoxia group,hypoxia group,normoxic control group,hypoxia + saline group and hypoxia + lithium chloride group.Hypoxia group was treated with 10％ oxygen concentration for 4 weeks.Hypoxia + saline group and hypoxia + lithium chloride group were intraperitoneal injection of saline and lithium chloride.Electrophysiology and cardiac catheterization were used to assess arrhythmias,heart rate and ejection fraction.The expression of Cx43,phosphorylated glycogen synthase kinase 3β(p-GSK-3β) and glycogen synthase kinase 3β (GSK-3β) were detected by Western blot.Results Compared with the normoxia group,the hypoxia group had a faster heart rate [(448 ± 18) bpm vs.(401 ± 13) bpm,P＜0.05),and the ejection fraction was decreased [(56±5)％ vs.73±4)％,P＜0.05],arrhythmia score increased [(3.4±0.5)％ vs.(0.6±0.5)％,P＜0.05],Cx43 expression was decreased.Compared to hypoxia + normal saline group,the heart rate decreased[(412±11)bpm vs.(454±18)bpm,P＜0.05],ejection fraction increased[(69±3)％ vs.(55±4)％,P＜0.05],the score of arrhythmia decreased [(1.8±0.4) ％ vs.(3.0±0.7)％,P＜0.05] in hypoxia + lithium chloride group,the expression of Cx43 and the rate of p-GSK-3β to GSK-3β were increased.Conclusion During the chronic hypoxia,lithium chloride can sustain the gap junction through inhibition of GSK-3β signaling way,which can also reduce the rate of arrhythmia.