Effect of Empagliflozin on ventricular arrhythmias in rats with myocardial infarction by dose-dependent regulation of autophagy. [J]. Journal of Southwest Medical University 46(4):314-319(2023)
DOI:
Effect of Empagliflozin on ventricular arrhythmias in rats with myocardial infarction by dose-dependent regulation of autophagy. [J]. Journal of Southwest Medical University 46(4):314-319(2023) DOI: 10.3969/j.issn.2096-3351.2023.04.008.
Effect of Empagliflozin on ventricular arrhythmias in rats with myocardial infarction by dose-dependent regulation of autophagy
Objective To investigate the effect of Sodium-glucose co-transporter 2 inhibitor
Empagliflozin(EMPA)
on ventricular arrhythmias (VAs) in myocardial infarction (MI) rats and its possible mechanism. Methods The MI models of non-diabetic male SD rats were established by ligation of the anterior descending branch of the left coronary artery
and the rats were divided into MI group
low-EMPA group (10 mg/kg/d) and high-EMPA group(30mg/kg). The Sham group underwent thoracotomy but was not treated with coronary ligation. Drug intervention continued for 4 weeks. After 4 weeks
echocardiography was performed
the induction rate of VAs was detected by burst stimulation. Myocardial morphology was observed by HE staining
and autophagy related proteins P62
Beclin-1
LC3I and LC3II were detected by western blot. Results ① Ultrasonography: Compared with Sham group
LVAWT
IVST and EF in MI group were significantly decreased (P < 0.05)
LVEDD and LVEDS were significantly increased (P < 0.05)
with no statistically significant differences in LVPWT(P > 0.05). Compared with the MI group
LVAWT
IVST and EF in low-EMPA group and high-EMPA group were significantly increased (P < 0.05)
whereas LVEDD and LVEDS were significantly decreased (P < 0.05)
with no statistically significant differences in LVPWT (P > 0.05). While LVAWT
LVPWT and EF of low-EMPA group and high-EMPA group had no statistical difference (P > 0.05). The IVST of low-EMPA group was significantly higher than that of high-EMPA group (P < 0.05). The LVEDS and LVEDD of low-EMPA group were significantly lower than those of high-EMPA group (P < 0.05). ②VAs scores: Compared with the Sham group
VAs scores in MI group were significantly higher (P < 0.05); Compared with the MI group
VAs scores in low-EMPA group and high-EMPA group were significantly decreased(P < 0.05)
with the effect of the high-EMPA group being more obvious
but there was no significant difference in VAs scores between the low-EMPA group and high-EMPA group(P > 0.05). ③ Western blot: Compared with the Sham group
the expression of P62 in the MI group increased (P < 0.05)
while Beclin-1
LC3II expression decreased (P < 0.05). Compared with the MI group
the expression of P62 in the low-EMPA and high-EMPA groups decreased(P < 0.05)
with Beclin-1 and LC3II expression increasing (P < 0.05). Compared with the high-EMPA group
the expression of P62 in the high-EMPA group decreased (P < 0.05)
with Beclin-1 and LC3II expression increasing(P < 0.05). Conclusion EMPA could significantly improve the induction rate of VAs dose-dependently in rats with myocardial infarction
and its possible mechanism was to improve cardiac function and cardiac structure remodeling and activate myocardial autophagy.
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Related Author
YE Qiang
ZHA Kelan
YANG Ruixue
JING Yuling
LI Tao
CHEN Wen
审校
冯淬灵
Related Institution
Department of Cardiology,Affiliated Hospital of Southwest Medical University
Key Laboratory of Medi⁃ cal Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province,Collaborative Inno⁃ vation Center for Prevention and Treatment of Cardiovascular Disease,Institute of Cardiovascular Research,Southwest Medical University
Department of Pulmonary disease,Qingyang Hospital of Traditional Chinese Medicine
Beijing University of Traditional Chinese Medicine
School of In⁃ tegrated Traditional Chinese and Western Medicine,Southwest Medical University