Neuregulin‑1 protects cardiac function in septic rats through multiple targets based on endothelial cells

Kang,Wen; Cheng,Yue; Zhou,Fang; Wang,Long; Zhong,Liang; Li,Hai Tao; Wang,Xi; Dang,Song; Wang,Xin

doi:10.3892/ijmm.2019.4309

Neuregulin‑1 protects cardiac function in septic rats through multiple targets based on endothelial cells

Authors:
- Wen Kang
- Yue Cheng
- Fang Zhou
- Long Wang
- Liang Zhong
- Hai Tao Li
- Xi Wang
- Song Dang
- Xin Wang
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Affiliations: Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Anesthesiology, Wuhan Medical and Healthcare Center for Women and Children, Wuhan, Hubei 430060, P.R. China, Department of Cardiology, Hainan General Hospital, Haikou, Hainan 570100, P.R. China
Published online on: August 8, 2019 https://doi.org/10.3892/ijmm.2019.4309
Pages: 1255-1266
Copyright: © Kang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The primary mechanism underlying sepsis‑induced cardiac dysfunction is loss of endothelial barrier function. Neuregulin‑1 (NRG‑1) exerts its functions on multiple targets. The present study aimed to identify the protective effects of NRG‑1 in myocardial cells, including endothelial, anti‑inflammatory and anti‑apoptotic effects. Subsequent to lipopolysaccharide (LPS)‑induced sepsis, rats were administered with either a vehicle or recombinant human NRG‑1 (rhNRG‑1; 10 µg/kg/day) for one or two days. H9c2 cardiomyoblasts were subjected to LPS (10 µg/ml) treatment for 12 and 24 h with or without rhNRG‑1 (1 µg/ml). Survival rates were recorded at 48 h following sepsis induction. The hemodynamic method was performed to evaluate cardiac function, and myocardial morphology was observed. Von Willebrand Factor levels were detected using an immunofluorescence assay. Serum levels of tumor necrosis factor α, interleukin‑6, intercellular cell adhesion molecule‑1 and vascular endothelial growth factor were detected using an enzyme‑linked immunosorbent assay; the reductase method was performed to detect serum nitric oxide levels. Apoptosis rates were determined using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Ras homolog family member A (RhoA) and Rho‑associated protein kinase 1 (ROCK1) protein levels were assessed using western blotting. Transmission electron microscopy was used to observe endothelial cells and myocardial ultrastructure changes. Results revealed that NRG‑1‑treated rats displayed less myocardial damage compared with sham rats. NRG‑1 administration strengthened the barrier function of the vasculature, reduced the secretion of endothelial‑associated biomarkers and exerted anti‑inflammatory and anti‑apoptotic effects. In addition, NRG‑1 inhibited RhoA and ROCK1 signaling. The results revealed that NRG‑1 improves cardiac function, increases the survival rate of septic rats and exerts protective effects via multiple targets throughout the body. The present results contribute to the development of a novel approach to reverse damage to myocardial and endothelial cells during sepsis.

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