血清总胆汁酸水平在ApoE-/-小鼠心律失常发生中的作用

doi:10.13481/j.1671-587X.20250403

摘要/Abstract

摘要：

目的探讨长期高脂饮食引起载脂蛋白E敲除（ApoE^-/-）小鼠血清胆汁酸水平改变在室上心律失常（SVA）发生中的作用，并探讨其作用机制。方法将20只ApoE^-/-小鼠随机分为正常饲料组和高脂饲料（HFD）组，每组10只，饲养20周后，采用体表心电图检查2组小鼠心脏电生理，超声心动图检测2组小鼠心脏收缩功能和结构，酶联免疫吸附试验（ELISA）检测2组小鼠血清中血脂、总胆汁酸（TBA）和炎症因子水平，苏木精-伊红（HE）染色检测2组小鼠心脏炎症反应，Masson染色观察2组小鼠心肌纤维化程度。结果 HFD组小鼠出现交界区早搏（JPB）/交界区心动过速（JT）4例、房性早搏（PAC）1例和室性早搏（PVC）1例，而正常饲料组小鼠仅出现JPB/JT和PAC各1例。与正常饲料组比较，HFD组小鼠心率明显降低（P<0.05），收缩末期容积（ESV）、心室去极时间（QRS）和心室去极和复极总时间（QT）间期明显延长（P<0.05），射血分数（EF）和短轴缩短率（FS）降低（P<0.05），舒张末期容积（EDV）升高（P<0.05），但组间收缩末期容积（ESV）比较差异无统计学意义（P>0.05），左心室舒张末期内径（LVIDd）和左心室收缩末期内径（LVIDs）增加（P<0.05），血浆中总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL-c）、低密度脂蛋白（LDL-c）水平和体质量差异无统计学意义（P>0.05），TBA水平升高（P<0.05），白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）、单核细胞趋化蛋白（MCP-1）和趋化因子C-X-C基序配体1（CXCL-1）差异均无统计学意义（P>0.05）。与正常饲料组比较，HFD组小鼠白细胞介素1β（IL-1β）水平差异无统计学意义（P>0.05）。HE染色，HFD与正常饲料组小鼠炎性细胞浸润相似。Masson染色，与正常饲料组比较，HFD组小鼠纤维化有增加趋势，但心肌纤维化面积组间差异无统计学意义（P>0.05）。结论长期高脂饮食可升高ApoE^-/-小鼠血清TBA水平，可能引起SVA。

关键词: 高脂饮食, 总胆汁酸, 室上心律失常, 炎症因子, 心肌纤维化

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

中图分类号:

R542.22

岳星,李雪梅,张寒潇,左川弋,朱莉娟,吕菁,张承舜,曹新. 血清总胆汁酸水平在ApoE^-/-小鼠心律失常发生中的作用[J]. 吉林大学学报(医学版), 2025, 51(4): 879-886.

Xing YUE,Xuemei LI,Hanxiao ZHANG,Chuanyi ZUO,Lijuan ZHU,Jing LYU,Chengshun ZHANG,Xin CAO. Role of serum total bile acid level in development of arrhythmia in ApoE^-/- mice[J]. Journal of Jilin University(Medicine Edition), 2025, 51(4): 879-886.

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Group	EF（η/%)	FS（η/%)	EDV（V/μL)	ESV（V/μL)	LVIDd（l/mm)	LVIDs（l/mm)	IVSd（l/mm)	LVPWd（l/mm)
Normal diet	77.59±2.55	40.48±2.38	138.00±27.54	41.00±31.78	3.77±0.28	2.29±0.16	0.36±0.05	0.39±0.07
HFD	70.05±4.77^**	34.43±3.66^**	184.30±33.04^*	55.70±11.34	4.18±0.28^*	2.74±0.17^**	0.36±0.05	0.40±0.00

Group	TC[c_B/(mmol·L^-1)]	TG[ρ_B/(μg·L^-1)]	HDL[ρ_B/(mg·dL^-1)]	LDL[c_B/(mmol·L^-1)]	Body weight （m/g）
Normal diet	4.67±0.70	165.73±48.08	61.31±9.07	5.38±0.80	28.34±0.93
HFD	4.39±0.74	159.61±51.51	58.15±4.84	5.59±0.58	27.61±1.89

Group	TBA[c_B/(μmol·L^-1)]	IL-1β[ρ_B/(ng·L^-1)]	IL-6[ρ_B/(ng·L^-1)]	TNF-α[ρ_B/(ng·L^-1)]	MCP-1[ρ_B/(ng·L^-1)]	CXCL-1[ρ_B/(ng·L^-1)]
Normal diet	6.38±1.27	59.36±17.53	46.69±10.44	421.55±50.78	19.04±2.23	115.45±20.09
HFD	7.82±1.27^*	69.79±9.49	43.59±12.38	419.35±48.70	18.88±1.81	106.61±13.83