Effects of NaHS and hydroxylamine on the expressions of brain-derived neurotrophic factor and its receptors in rats after cardiac arrest and cardiopulmonary resuscitation

Jiyan Lin,Mandong Pan,Zhihong Xu,Siyao Liu,Wang Lu,Weicheng Wu

doi:10.1186/s13049-018-0577-z

Abstract

BackgroundH2S can also protect nerve cells. The objective of the study is to investigate the effects of hydrogen sulfide (H2S) on the expressions of brain-derived neurotrophic factor (BDNF) and its receptors, tyrosine protein kinase B (TrkB) and p75 neurotrophin receptor (p75NTR), in brain tissues of rats with cardiac arrest and cardiopulmonary resuscitation (CA/CPR) following the restoration of spontaneous circulation (ROSC).MethodsRats (n = 240) with CA/CPR were divided into three groups: Intervention (n = 80) that received sodium hydrosulfide (NaHS, 14 μmoL/kg·d) intervention after ROSC; Inhibition (n = 80) that received hydroxylamine (40 μmoL/kg·d) intervention after ROSC; and Control (n = 80) that received saline after ROSC. Kaplan-Meyer analysis was used to analyze the survival data. Quantitative real-time PCR (q-PCR), Western blot, immunohistochemistry and IODs (integrated optical density) were performed to determine the mRNA and protein expressions of BDNF, TrkB and p75NTR in rat brain tissues.ResultsSurvival rate of the three groups had significant difference (χ2 = 28.376, p = 0.000). The Intervention group had the highest survival rate (82.5%), while the Inhibition group had the lowest survival rate (62.5%). The mRNA and protein levels of BDNF and TrkB in the Intervention group were significantly higher compared to the Control group (p < 0.05); while the mRNA and protein levels of BDNF and TrkB in the Inhibition group was significantly lower than the Control group (p < 0.05) on days 1, 3, and 7. However, the mRNA and protein levels of p75NTR in the Intervention group were significantly lower than the Control group (p < 0.05); while the mRNA and protein levels of p75NTR in the Inhibition group were significantly higher than the Control group (p < 0.05) on days 1, 3, and 7.ConclusionNaHS treatment increases the survival rate of rats after CA and ROSC by upregulating the expression and activation of BDNF and its receptor TrkB, and down-regulating p75NTR expression.

Highlights

General physiological characteristics of rats A total of 240 rats were used for the cardiac arrest and cardiopulmonary resuscitation (CA/cardiopulmonary resuscitation (CPR)) model
Because the H2S formation in the Inhibition group was inhibited by hydroxylamine (Fig. 1), the serum H2S concentrations in Inhibition group was significantly lower than the Control group (p < 0.05), and were maintained at a low level during the 7-d observation period
Our results indicate that intravenous injection of NaHS·H2O effectively increased the H2S concentration in the serum of CA/CPR rats after restoration of spontaneous circulation (ROSC); while hydroxylamine inhibited H2S formation

Summary

Introduction

The objective of the study is to investigate the effects of hydrogen sulfide (H2S) on the expressions of brain-derived neurotrophic factor (BDNF) and its receptors, tyrosine protein kinase B (TrkB) and p75 neurotrophin receptor (p75NTR), in brain tissues of rats with cardiac arrest and cardiopulmonary resuscitation (CA/CPR) following the restoration of spontaneous circulation (ROSC). There are two types of NT receptors: the original high-affinity myosin receptor kinase (tropomyosin receptor kinase, Trk) and low-affinity receptor of p75 (p75 NT receptor, p75NTR) Both receptors are involved in the regulation of growth, differentiation, repair, apoptosis and survival of cells [5]. It promotes neuronal survival and growth, induces neuronal apoptosis [9], inhibits the axonal growth of neurons [10], and regulates cell cycle [11]. P75NTR mediates both “positive” and “negative” effects, it mainly mediates “negative” pro-apoptotic effects [12]

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