Journal of Jilin University(Medicine Edition) ›› 2021, Vol. 47 ›› Issue (6): 1353-1361.doi: 10.13481/j.1671-587X.20210603

• Research in basic medicine • Previous Articles     Next Articles

Effect of Shenxianshengmai Oral Liquid on ROS expression in mice with sick sinus syndrome and its regulation on HCN4 ion channel

Dan MAO1,Zhishuang LI1,Jiaxin CHENG1,Ping HOU2()   

  1. 1.First Clinical College,Liaoning University of Traditional Chinese Medicine,Shenyang 110032,China
    2.Second Department of Cardiology,Affiliated Hospital,Liaoning University of Traditional Chinese Medicine,Shenyang 110032,China
  • Received:2021-03-16 Online:2021-11-28 Published:2021-12-14
  • Contact: Ping HOU E-mail:houping57@163.com

Abstract: Objective

To investigate the effect of Shenxianshengmai Oral Liquid on the release of reactive oxygen species (ROS) in sinoatrial node tissue of the sinoatrial node syndrome (SSS) mice and its regulation on cyclic nucleotide regulated cation channel protein subtype 4 (HCN4) ion channel, and to explore the mechanism of Shenxianshengmai Oral Liquid in improving the SSS.

Methods

A total of 30 C57B6 mice were randomly divided into sham operation group,SSS group,and Shenxianshengmai Oral Liquid treatment (SXSM) group, and there were 10 mice in each group. The SSS mice model was established by pumping angiotensinⅡ(ANGⅡ) with the Alzet osmotic pressure pump.The mice in SXSM group were given 0.2 mL of Shenxianshengmai Oral Liquid per day for 28 d. The electrocardiogram of the mice in various groups was observed and the heart rates were analyzed; HE and Masson staining methods were used to observe the pathomorphology of sinoatrial node tissue of the mice in various groups,immunofluorescence method was uesd to detect the levels of ROS and HCN4 in sinoatrial node tissue of the mice in various groups; Real-time fluorescence quantitative PCR (RT-qPCR) method was used to detect the expression levels of voltage-gated Na+α subunit (SCN5A), L-type voltage dependent calcium channels α 1C subunit protein (CACNα1C) and voltage dependent calcium channel α1G subunit protein (CACNα1G) mRNA in sinoatrial node tissue of the mice in various groups; Western blotting method was used to detect the expression levels of SCN5A,CACNα1C,CACNα1G,and HCN4 proteins in sinoatrial node tissue of the mice in various groups.

Results

Compared with sham operation group, the heart rate of the mice in SSS group was decreased significantly (P<0.05), the cells were dissolved and necrotic, there was no nucleus, and there was a large number of connective fiber tissue; the ROS level in sinoatrial node tissue was increased (P<0.05),the HCN4 level in sinoatrial node tissue was decreased (P<0.05), the expression levels of SCN5A mRNA and protein in sinoatrial node tissue were decreased significantly (P<0.05),the expression levels of CACNα1C and CACNα1G mRNA and proteins in sinoatrial node tissue were increased significantly (P<0.05),and the expression level of HCN4 protein in sinoatrial node tissue was decreased significantly (P<0.05);compared with SSS group, the heart rate of the mice in SXSM group was increased significantly(P<0.05),a small amount of connective fiber tissue showed hyperplasia, partial of the cells showed necrosis and dissolution, the ROS level in sinoatrial node tissue was decreased (P<0.05),the HCN4 level in sinoatrial node tissue was increased (P<0.05),the expression levels of SCN5A mRNA and protein in sinoatrial node tissue were increased (P<0.05),the expression levels of CACNα1C and CACNα1G mRNA and proteins in sinoatrial node tissue were decreased significantly (P<0.05),and the expression level of HCN4 protein in sinoatrial node tissue was increased significantly (P<0.05).

Conclusion

Shenxianshengmai Oral Liquid can increase the heart rate, inhibit the release of ROS in sinoatrial node tissue of the SSS mice, and inhibit the fibrosis of the sinoatrial nodes. The mechanism is related to the regulation of HCN4 ion channels.

Key words: Shenxianshengmai Oral Liquid, sick sinus syndrome, mitochondrial reactive oxygen species, cyclic nucleotide regulated cation channel protein subtype 4 ion channel

CLC Number: 

  • R285.5