Pioglitazone's Therapeutic Effect and Electrophysiological Mechanism on Rat Ventricular Arrhythmias Induced by β1-adrenergic Receptor Autoantibodies
10.3969/j.issn.1000-3614.2024.07.010
- VernacularTitle:吡格列酮治疗β1肾上腺素能受体自身抗体诱导的大鼠室性心律失常的作用和电生理机制研究
- Author:
Linqiang XI
1
;
Huaxin SUN
;
Luxiang SHANG
;
Qianhui WANG
;
Jie SONG
;
Na YANG
;
Xing ZHANG
;
Taiwaikuli DILARE
;
Rejiepu MANZEREMU
;
Ling ZHANG
;
Baopeng TANG
;
Xianhui ZHOU
Author Information
1. 新疆医科大学第一附属医院 心脏起搏与电生理科 新疆心电生理与心脏重塑重点实验室,乌鲁木齐 830054
- Keywords:
pioglitazone;
peroxisome proliferator-activated receptor;
ventricular arrhythmia;
β1 adrenergic receptor antibody;
mitochondria
- From:
Chinese Circulation Journal
2024;39(7):716-724
- CountryChina
- Language:Chinese
-
Abstract:
Objectives:This study aims to explore the effects of pioglitazone on the attenuation of ventricular arrhythmias(VAs)induced by β1-adrenergic receptor autoantibodies(β1AAb)and its potential mechanisms. Methods:48 SD rats were uniformly randomly divided into four groups using number table:control group received vehicle injection,β1AAb group received back multi-point injection of β1AR-ECLⅡ antigen peptide with adjuvant,2 mg/(kg·time),pioglitazone group received pioglitazone gavage for 2 weeks after 8 weeks of immunization,4 mg/(kg·d),and GW9662 group received pioglitazone+GW9662 intraperitoneal injection for 2 weeks after 8 weeks of immunization,1 mg/(kg·d).Powerlab recorded electrocardiograms and blood collection every 2 weeks.Baseline and week 10 echocardiography were recorded,followed by electrophysiology,histopathology,immunohistochemical staining,and electron microscopy examination after 10 weeks. Results:Compared to control group,β1AAb group showed a higher incidence of ventricular arrhythmias,shorter ventricular effective refractory period(VERP),longer action-recovery interval(ARI),lower left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS),lower positive staining area ratio of glucose transporter 1(GLUT1)and carnitine palmitoyltransferase 1a(CPT1a),all P＜0.05.Mitochondrial morphology abnormalities and network damage were also significantly observed(P＜0.05).In contrast to β1AAb group,pioglitazone group showed a reduced incidence of ventricular arrhythmias,prolonged VERP,shortened ARI,recovered LVEF and LVFS,increased the positive staining area ratio of GLUT1 and CPT1a,all P＜0.05.Improvement was observed in mitochondrial morphology abnormalities and network damage(P＜0.05).Compared to pioglitazone group,GW9662 group exhibited a higher incidence of ventricular arrhythmias,shorter VERP,and longer ARI,lower LVEF and LVFS,lower positive staining area ratio of GLUT1 and CPT1a,all P＜0.05.Mitochondrial morphology abnormalities and network damage did not recover(P＜0.05). Conclusions:Pioglitazone can reduce VAs induced by β1AAb,improve ventricular electrical conduction and activation recovery time heterogeneity,and mitigate ventricular remodeling caused by β1AAb at the tissue pathology level,accompanied by upregulation of ventricular cardiomyocyte glucose and lipid transport channel proteins and repair of damaged mitochondrial networks.
