Brain-Derived Neurotrophic Factor Attenuates Septic Myocardial Dysfunction via eNOS/NO Pathway in Rats.

Ni Zeng,Wei Ruan,Feng Xiao,Weifeng Yao,Suobei Li,Junmei Xu

doi:10.1155/2017/1721434

Abstract

Sepsis-induced myocardial dysfunction increases mortality in sepsis, yet the underlying mechanism is unclear. Brain-derived neurotrophic factor (BDNF) has been found to enhance cardiomyocyte function, but whether BDNF has a beneficial effect against septic myocardial dysfunction is unknown. Septic shock was induced by cecal ligation and puncture (CLP). BDNF was expressed in primary cardiomyocytes, and its expression was significantly reduced after sepsis. In rats with sepsis, a sharp decline in survival was observed after CLP, with significantly reduced cardiac BDNF expression, enhanced myocardial fibrosis, elevated oxidative stress, increased myocardial apoptosis, and decreased endothelial nitric oxide (NO) synthase (eNOS) and NO. Supplementation with recombined BDNF protein (rhBDNF) enhanced myocardial BDNF and increased survival rate with improved cardiac function, reduced oxidative stress, and myocardial apoptosis, which were associated with increased eNOS expression, NO production, and Trk-B, a BDNF receptor. Pretreatment with NOS inhibitor, N (omega)-nitro-L-arginine methyl ester, abolished the abovementioned BDNF cardioprotective effects without affecting BDNF and Trk-B. It is concluded that BDNF protects the heart against septic cardiac dysfunction by reducing oxidative stress and apoptosis via Trk-B, and it does so through activation of eNOS/NO pathway. These findings provide a new treatment strategy for sepsis-induced myocardial dysfunction.

Highlights

Sepsis is identified as a systemic deleterious inflammatory response to infection or injury [1]
All data were described as mean ± standard error of measurement (SEM) and analyzed using GraphPad Prism 6
In primary cardiomyocytes isolated from rats, we showed that Brain-derived neurotrophic factor (BDNF) was expressed in cardiomyocytes and was reduced after cecal ligation and puncture (CLP) (Figure 1(b))

Summary

Introduction

Sepsis is identified as a systemic deleterious inflammatory response to infection or injury [1]. Cardiac dysfunction is the leading cause of death in patients with sepsis [3,4,5,6]. Septic myocardial dysfunction is complicated and multifactorial, which involved persistent inflammation-induced microlesions of endothelium and endocardium, alterations in intracellular calcium homeostasis, contractile dysfunction of the heart, increase of reactive oxygen species (ROS), and apoptosis [9, 10]. Oxidative stress has been considered to play a critical role in the progression of sepsis-induced myocardial dysfunction [11,12,13]. Ample evidence has demonstrated protective effects of antioxidant facilitation in sepsis, and reinforcement of myocardium endogenous antioxidant defense attenuates cardiac oxidative stress and preserves contractile reserve [11, 14,15,16]

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Results

Conclusion