Oxymatrine protects against sepsis-induced myocardial injury via inhibition of the TNF-α/p38-MAPK/caspase-3 signaling pathway

Zhang,Minghao; Wang,Xiuyu; Bai,Bin; Zhang,Rui; Li,Yunhong; Wang,Yin

doi:10.3892/mmr.2016.5250

Oxymatrine protects against sepsis-induced myocardial injury via inhibition of the TNF-α/p38-MAPK/caspase-3 signaling pathway

Authors:
- Minghao Zhang
- Xiuyu Wang
- Bin Bai
- Rui Zhang
- Yunhong Li
- Yin Wang
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Affiliations: Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China, Department of Endocrinology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
Published online on: May 11, 2016 https://doi.org/10.3892/mmr.2016.5250
Pages: 551-559

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Abstract

Oxymatrine (OMT), which is a quinolizidine alkaloid extracted from the traditional Chinese herb Sophora flavescens Aiton, is often used to treat various inflammatory diseases. The present study aimed to investigate the protective effects of OMT against septic shock‑induced myocardial injury in rats, and to determine the underlying mechanisms. In the present study, cecal ligation and puncture (CLP) was applied to generate a rat model of sepsis. The rats were randomly divided into six groups (n=8/group): Sham operation (CON) group, OMT control group, CLP model group, and CLP + OMT (high dose, 52 mg/kg; medium dose, 26 mg/kg; low dose, 13 mg/kg) groups. Cardiac function and histological alterations were analyzed by light microscopy and electron microscopy. Myocardial cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The mRNA and protein expression levels were examined by reverse transcription-polymerase chain reaction and western blotting, respectively. Furthermore, the levels of tumor necrosis factor (TNF)‑α in the myocardial tissue were determined by radioimmunoassay. The results demonstrated that OMT exhibited anti‑inflammatory properties, improved myocardial contractility and compliance, and significantly decreased pathological injury to rat myocardial ultrastructure. In addition, OMT significantly decreased heart rate and left ventricular end diastolic pressure, and increased mean arterial pressure, left intraventricular pressure change rate, and left ventricular end systolic pressure in rats following septic shock. Treatment with OMT attenuated the mRNA expression of lipopolysaccharide binding protein, cluster of differentiation 14, nuclear factor (NF)‑κB (p65), TNF‑α, p38‑mitogen‑activated protein kinase (MAPK) and caspase‑3, and decreased the protein expression of NF‑κB (p65), phosphorylated (p) NF‑κB inhibitor‑α, p‑p38‑MAPK caspase‑3 and TNF‑α in septic myocardial tissue. The present study concluded that OMT may offer substantial therapeutic potential for the treatment of septic shock‑induced myocardial injury by inhibiting the TNF-α/p38-MAPK/caspase-3 signaling pathway.

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