Effect of overexpression of tumor necrosis factor-α in failing heart on contractile function of diaphragm

VernacularTitle:心力衰竭鼠心脏肿瘤坏死因子α超量表达对膈肌收缩功能的影响
Author: Xia LI ; Hualan ZHOU ; Youdong HU ; Yan GUO
Publication Type:Journal Article
Keywords: Heart failure,congestive; Tumor necrosis factor-alpha; Oxidative stress
From: Chinese Journal of Geriatrics 2011;30(3):237-240
CountryChina
Language:Chinese
Abstract: Objective To study the effect of overexpression of tumor necrosis factor-α (TNFα) in failing heart on contractile function of mouse diaphragm. Methods Diaphragms excised from transgenic mice with cardiac specific overexpression of TNF-α and from wild-type littermate controls were studied in vitro with direct electrical stimulation. Cytosolic oxidant levels were measured with 2',7'-dichlorofluorescin diacetate (DCFH-DA). Emissions of the oxidized product were detected by fluorescence microscopy. Results The diaphragm contractile force in transgenic animals with heart failure was 47% less than in controls [(13. 2±0. 8) N/cm2 vs. (25.1±0. 6) N/cm2 , P＜O. 01]. The weakness was associated with greater intracellular oxidant levels (P＜0. 05) and was partially reversed by 30-minute incubation with the antioxidant N-acetylcysteine (NAC) 10 mmol/L ( P ＜ 0. 01 ).Exogenous TNF-a 500 mmol/L increased oxidant production in diaphragm of wild-type mice and caused weakness that was inhibited by NAC. Conclusions Overexpression of TNF in failing heart causes oxidative stress which leads contractile dysfunction in mouse diaphragm.