The Effect of Overexpression of Nav1.5 on Apoptosis and Fibrosis of Cardiomyocytes in Mice with Long QT Syndrome Induced by Sea Anemone Toxin
LI Peicheng
LIU Hui
LI Yanan
LI Xiaolei
LIU Peng
KONG Linghao
Abstract：Objective:To investigate the regulatory effects of overexpression of sodium channel protein 1.5(Nav1.5)on the apoptosis and fibrosis of cardiomyocytes in mice with long QT syndrome induced by sea anemone toxin.Methods:Twenty-four SPF-grade 8-week-old male C57BL/6J mice were randomly divided into the control group,the sea anemone toxin group,the pcDNA-Nav1.5+sea anemone toxin group,and the pcDNA-null+sea anemone toxin group according to the random number table method,with 6 mice in each group.The sea anemone toxin group was injected with 10 nmo/L sea anemone toxin solution at a dose of 0.1 mL via the tail vein every day.The mice in the control group were injected with an equal volume of normal saline intravenously every day.The mice in the pcDNA-Nav1.5+sea anemone toxin group were intravenously injected with a 10 nmol/L sea anemone toxin solution and 0.1 mL of a mixed solution composed of 50 μg/L pcDNA3.1(+)and overexpressed Nav1.5.The pcDNA-null+sea anemone toxinin group was injected with 10 nmol/L sea anemone toxinin solution via the tail vein,and mixed with 50 μg/L pcDNA3.1(+)empty vector(pcDNA-null)solution in a 0.1 mL volume.Each group was injected once daily and the injections were carried out continuously for 7 days.The expression levels of Nav1.5,cleaved-Caspase-3,B-cell lymphoma-2 protein(Bcl-2),Bcl-2-associated X protein(Bax),type Ⅰ collagen(COL1A1),type Ⅲ collagen(COL3A1),alpha-subtype of smooth muscle actin(Alpha-Smooth Muscle Actin,α-SMA),TGF-β1,phosphorylated Smad3(p-Smad3),and Smad3 in cardiomyocytes were detected by Western Blot method.The apoptosis rate of cells in each group of myocardial tissues was detected by flow cytometry.Results:Compared with the control group,the mice in the hyaluronin group showed prolonged QT intervals,increased apoptosis rate of myocardial cells,upregulated expression of cleaved-Caspase-3 and Bax proteins,downregulated expression of Bcl-2 protein,upregulated expression of myocardial fibrosis-related proteins COL1A1,COL3A1,and α-SMA,and upregulated expression of TGF-β1 and p-Smad3 proteins(P＜0.05).After overexpression of Nav1.5,all these changes were significantly reversed.Compared with the pcDNA-null+sea anemone toxin group,the apoptosis rate of myocardial cells in the pcDNA-Nav1.5+sea anemone toxin group decreased,the expression of cleaved-Caspase-3 and Bax proteins was downregulated,the expression of Bcl-2 protein upregulated,the expressions of myocardial fibrosis-related proteins COL1A1,COL3A1,and α-SMA upregulated,and the expressions of TGF-β1 and p-Smad3 proteins downregulated(P＜0.05).Conclusion:Overexpression of Nav1.5 can effectively inhibit apoptosis and fibrosis of cardiomyocytes in mice with long QT syndrome induced by oculin.The mechanism may be related to the regulation of the TGF-β1/Smad3 signaling pathway.
Keywords：long QT syndromesodium channel protein 1.5cardiomyocytes apoptosisfibrosissea anemone toxin
Publication Date：2026-03-10
Online Publishing Date：2026-03-24(First online date of this platform, not the publication date of the document)
Pages：7( 665-671 )