Neuregulin-1 inhibits myocardial cell apoptosis by attenuating mitochondrial stress in rats with heart failure after myocardial infarction
10.3760/cma.j.issn.0254-9026.2013.09.023
- VernacularTitle:纽兰格林改善线粒体应激抑制心肌梗死后心力衰竭大鼠细胞凋亡
- Author:
Yongfang GUO
;
Yi AN
;
Jian LI
;
Xiaoxia ZHANG
;
Xuesi WU
- Publication Type:Journal Article
- Keywords:
Intercellular signaling peptides and proteins;
Heart failure;
Apoptosis;
Mitochondria
- From:
Chinese Journal of Geriatrics
2013;32(9):1001-1005
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effect of Neuregulin-1 (NRG) on rat heart failure(HF) after myocardial infarction,and to investigate the underlying mechanism involving in NRG-mediated cardioprotection.Methods 60 adult Wister rats underwent sham operation (n=12) or coronary ligation (n=48) to induce HF.Four weeks after ligation,28 animals with HF were randomly divided into NRG group (rats received rhNRG-1 10 μg · kg-1 · d-1 intravenously for 10 days) or HF group (rats received an equal volume of water intravenously for 10 days).Left ventricular function was detected by echocardiography.Mitochondrial ultrastructure in non-infarcted myocardium was observed by transmission electronic microscopy.Cell apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay.Mitochondrial membrane potential was measured by immunofluorescence method.Caspase-3 activity was determined by commercial kit.The expression of cytochrome C protein in cytoplasm was detected by Western blot.Results Compared with HF group,the left ventricular end-systolic diameter was decreased,and left ventricular ejection fraction and fractional shortening were increased in NRG group (P＜0.05 or 0.01).Apoptosis index was reduced inNRG group as compared with HFgroup [(18.1±3.0)％ vs.(11.9±1.4)％,P＜0.01].Mitochondrial membrane potential was increased and the release of cytochrome c in cytoplasm was reduced in NRG group as compared with HF group [(249.8±7.4) mV vs.(222.2±7.5) mV,(0.356±0.024) vs.(0.664±0.085),both P＜0.01].Caspase-3 activity was decreased in NRG group as compared with HF group (P＜0.01).Conclusions NRG attenuats mitochondrial stress and inhibits myocardial cells apoptosis in heart failure rats after myocardial infarction,which may play an important role in the cardioprotection by NRG.
