The effect of tumor necrosis factor-¦Á inhibitor soon after hypoxia-ischemia on heart in neonatal rats

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• 作者：Belgin B&uuml ; y&uuml ; kakilli^a ; ^{bbuyukakilli@yahoo.com} ; Aytu? Atici^b ; Aziz Ö ; zkan^b ; Ebru Balli^c ; Sevgi G&uuml ; ne?^a ; Ali Haydar Turhan^b ; Olgu Hallioglu^d ; Arzu Kanik^e
• 关键词：Hypoxia ; Ischemia ; Etanercept ; Myocardial contractions ; Heart ultrastructure
• 刊名：Life Sciences
• 出版年：2012
• 出版时间：6 June, 2012
• 年：2012
• 卷：90
• 期：21-22
• 页码：838-845
• 全文大小：1978 K

文摘

Aims

Perinatal hypoxic-ischemic insult has acute and long term deleterious effects on many organs including heart. Although tumor necrosis factor alpha (TNF-¦Á) has been reported to increase soon after hypoxia, the inhibition of this mediator has not been documented. The aim of this study was to investigate the effects of a TNF-¦Á inhibitor (etanercept) on contractility and ultrastructure of rat heart muscles exposed to hypoxia-ischemia during neonatal period.

Main methods

Forty-five seven-day old rats divided into three groups were included in this study. The right carotid arteries of Saline and Etanercept groups of rats were ligated and kept in a hypoxia chamber containing 8 % oxygen for 2 h. Immediately after hypoxia, while Etanercept group was administered 10 mg/kg etanercept, Saline group had only saline intraperitoneally. The carotid arteries of rats in Sham group were located without ligation and hypoxia. Mechanical activity of heart was recorded and tissue samples were examined by electron microscopy in the sixteenth week following the hypoxia-ischemia.

Key findings

While atrial contractile force in Etanercept group was similar to Sham group, there was significant decrease in Saline group (p < 0.001). However, there was only non-significant decrease in ventricular contractility of Saline group comparing to Sham group (p &gt; 0.05). After hypoxia-ischemia, ultrastructural degenerative changes and mitochondrial damage in atriums of Etanercept group were significantly less severe than Saline group.

Significance

This study demonstrated that neonatal hypoxia-ischemia caused long term cardiac dysfunction and ultrastructural degenerative changes in the heart of rats. TNF-¦Á inhibitor administration soon after hypoxia-ischemia may have heart protective effect.