Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Surgery. 2011 Aug;150(2):339-46. doi: 10.1016/j.surg.2011.05.018.
The activation of the epidermal growth factor family of receptors may improve cardiac protection after injury. One epidermal growth factor family ligand, transforming growth factor-alpha, promotes wound healing in multiple tissues in response to oxidative injury and might confer resistance to myocardial depressant factors, although the role of transforming growth factor-alpha in myocardial ischemia/reperfusion injury is unknown. We hypothesized that preischemic infusion of transforming growth factor-alpha would improve myocardial functional recovery after acute ischemia/reperfusion.
The hearts from adult male rats were isolated and perfused via the Langendorff model. Immediately prior to ischemia, the hearts received an intracoronary infusion of either vehicle or transforming growth factor-alpha (1 ng, 10 ng, or 100 ng). After reperfusion, the hearts were assessed for activation of the prosurvival pathway, Akt.
Infusion of transforming growth factor-alpha did not confer any additional functional protection compared with the vehicle, but myocardial tissue analysis revealed significantly increased activation of the Akt pathway in both the 10-ng and 100-ng groups.
Preischemic infusion of transforming growth factor-alpha does not improve myocardial functional recovery after ischemia/reperfusion injury. Whereas transforming growth factor-alpha treatment does affect actions at the molecular level, these actions do not translate into an observable functional effect. This lack of improvement may point to a relative unimportance of transforming growth factor-alpha in myocardial signaling compared with other epidermal growth factor ligands.
表皮生长因子家族受体的激活可能会改善损伤后的心脏保护作用。表皮生长因子家族的一种配体转化生长因子-α，在应对氧化损伤时可促进多种组织的伤口愈合，并且可能对抗心肌抑制因子，尽管转化生长因子-α在心肌缺血/再灌注损伤中的作用尚不清楚。我们假设，缺血前给予转化生长因子-α可改善急性缺血/再灌注后的心肌功能恢复。
成年雄性大鼠的心脏通过 Langendorff 模型进行分离和灌注。在缺血之前，心脏接受了冠状动脉内输注载体或转化生长因子-α（1ng、10ng 或 100ng）。再灌注后，评估心脏的促生存途径 Akt 的激活情况。
与载体相比，转化生长因子-α的输注并未提供任何额外的功能保护，但心肌组织分析显示，10ng 和 100ng 组 Akt 途径的激活明显增加。
缺血前给予转化生长因子-α并不能改善缺血/再灌注损伤后的心肌功能恢复。虽然转化生长因子-α的治疗确实会影响分子水平的作用，但这些作用并不能转化为可观察到的功能效果。这种改善的缺乏可能表明与其他表皮生长因子配体相比，转化生长因子-α在心肌信号转导中的相对不重要性。
