Abstract:

Objective To discuss the role of changes of serum total bile acid （TBA） levels induced by long-term high-fat diet in the occurrence of supraventricular arrhythmia （SVA） in the apolipoprotein E knockout （ApoE^-/-） mice， and to clarify its mechanism. Methods Twenty ApoE^-/- mice were randomly divided into normal diet group and high-fat diet （HFD） group （n=10）； after 20 weeks of feeding， surface electrocardiogram was used to detect cardiac electrophysiology of the mice in various groups； echocardiography was used to detect cardiac systolic function and structure in the mice in various groups； enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of blood lipids， total bile acid （TBA） and inflammatory factors in the mice in various groups； hematoxylin-eosin （HE） staining was used to detect cardiac inflammatory response in the mice in various groups； Masson staining was used to observe myocardial fibrosis degree in the mice in various groups. Results Compared with normal diet group， 4 cases of junctional premature beat （JPB）/junctional tachycardia （JT）， 1 case of premature atrial contraction （PAC） and 1 case of premature ventricular contraction （PVC） were found in HFD group， while only 1 case of JPB/JT and 1 case of PAC were found in normal diet group. Compared with normal diet group， the heart rate of the mice in HFD group was significantly decreased （P<0.05）； the QRS and QT intervals were significantly prolonged（P<0.05）； the ejection fraction （EF） and fractional shortening （FS） were significantly decreased （P<0.05）； the end-diastolic volume （EDV） was increased （P<0.05）， but there was no significant difference in end-systolic volume（ESV） between groups （P>0.05）； the left ventricular internal diameter at end-diastole （LVIDd） and left ventricular internal diameter at end-systole （LVIDs） were significantly increased （P<0.05）. There were no significant differences in plasma total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein （HDL-c） and low-density lipoprotein （LDL-c） levels and body weight between normal diet group and HFD group （P>0.05）. Compared with normal diet group， the TBA level of the mice in HFD group was significantly increased （P<0.05）. There were no significant differences in interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， monocyte chemoattractant protein-1 （MCP-1）， and C-X-C motif chemokine ligand 1 （CXCL-1） levels between HFD group and normal diet group. Compared with normal diet group， the interleukin-1β （IL-1β） level in HFD group showed an increasing trend， but there was no significant difference between groups （P>0.05）.The HE staining results showed that the inflammatory cell infiltration was similar between HFD group and normal diet group.The Masson staining results showed that compared with normal diet group， the fibrosis of the mice in HFD group showed an increasing trend， but there was no significant difference in myocardial fibrosis area between groups （P>0.05）. Conclusion Long-term high-fat diet may increase serum TBA level in ApoE^-/- mice， which may induce SVA.

Key words: High-fat diet, Total bile acid, Supraventricular arrhythmia, Inflammatory factor, Myocardial fibrosis