Vagal nerve stimulation protects cardiac injury by attenuating mitochondrial dysfunction in a murine burn injury model

Journal of Cellular and Molecular Medicine

Xiaojiong Lu¹  Todd Costantini¹  Nicole E. Lopez¹  Paul L. Wolf¹  Ann-Marie Hageny¹  James Putnam¹  Brian Eliceiri¹ 

[1] Division of Trauma, Surgical Critical Care and Burns, Department of Surgery, University of California San Diego Health Sciences, San Diego, CA, USA

关键词: burn injury;    vagal nerve stimulation;    cardiac injury;    mitochondrial dysfunction;    mitochondrial swelling;    PI3K/Akt;   

DOI  :  10.1111/jcmm.12049

来源: Wiley

【 摘 要 】

Abstract

Mitochondria play a central role in the integration and execution of a wide variety of apoptotic signals. In the present study, we examined the deleterious effects of burn injury on heart tissue. We explored the effects of vagal nerve stimulation (VNS) on cardiac injury in a murine burn injury model, with a focus on the protective effect of VNS on mitochondrial dysfunction in heart tissue. Mice were subjected to a 30% total body surface area, full-thickness steam burn followed by right cervical VNS for 10 min. and compared to burn alone. A separate group of mice were treated with the M₃-muscarinic acetylcholine receptor (M₃-AchR) antagonist 4-DAMP or phosphatidylinositol 3 Kinase (PI3K) inhibitor LY294002 prior to burn and VNS. Heart tissue samples were collected at 6 and 24 hrs after injury to measure changes in apoptotic signalling pathways. Burn injury caused significant cardiac pathological changes, cardiomyocyte apoptosis, mitochondrial swelling and decrease in myocardial ATP content at 6 and 24 hrs after injury. These changes were significantly attenuated by VNS. VNS inhibited release of pro-apoptotic protein cytochrome C and apoptosis-inducing factor from mitochondria to cytosol by increasing the expression of Bcl-2, and the phosphorylation level of Bad (pBad¹³⁶) and Akt (pAkt³⁰⁸). These protective changes were blocked by 4-DAMP or LY294002. We demonstrated that VNS protected against burn injury–induced cardiac injury by attenuating mitochondria dysfunction, likely through the M₃-AchR and the PI3K/Akt signalling pathways.

【 授权许可】

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© 2013 The Authors Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd

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