Department of Pharmacology, Faculty of Pharmacy, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, Debrecen, 4032, Hungary.
J Mol Neurosci. 2013 Jul;50(3):558-70. doi: 10.1007/s12031-013-9998-3. Epub 2013 Mar 17.
The present study demonstrates capacity of α-MSH to augment recovery from ischemia/reperfusion (I/R)-induced retinal damage in vivo and correlation of its protective effects with expression of heme oxygenase-1 (HO-1). Used techniques include ocular ischemia and reperfusion, electroretinography, histology, electron microscopy, and molecular-biological techniques. The results demonstrate the α-MSH-mediated inhibition of I/R-induced functional deterioration of the retina. Outcomes suggest that the protective effects of α-MSH occur mainly through HO-1-dependent pathways but HO-1-independent mechanisms may also contribute to protection. The observation that post-ischemic treatment with α-MSH exhibits therapeutic efficacy in the same range as pre-ischemic treatment, is a novel result. This outcome suggests a highly conserved protective role for α-MSH as a major stress response mechanism--and offers the possibility for development of novel therapeutic strategies utilizing this hormone, in particular in treatment of conditions resulting from I/R injury, such as deterioration of retinal microcirculation. The merit of the study lies in the fact that I/R injury contribute significantly to the severity of retinopathies. However, currently there are no evidence-based treatments for retinal I/R injury available for clinical use. Our finding suggests that α-MSH may have a very wide range of uses in the prevention of I/R-mediated pathologies.
本研究证明了 α-MSH 能够增强体内缺血/再灌注(I/R)诱导的视网膜损伤的恢复能力,并且其保护作用与血红素加氧酶-1(HO-1)的表达相关。所使用的技术包括眼缺血再灌注、视网膜电图、组织学、电子显微镜和分子生物学技术。研究结果表明,α-MSH 介导的抑制 I/R 诱导的视网膜功能恶化。研究结果表明,α-MSH 的保护作用主要通过 HO-1 依赖途径发生,但 HO-1 非依赖机制也可能有助于保护。值得注意的是,缺血后给予 α-MSH 的治疗效果与缺血前治疗效果相当,这是一个新的结果。这一结果表明,α-MSH 作为一种主要的应激反应机制,具有高度保守的保护作用,并为利用这种激素开发新的治疗策略提供了可能性,特别是在治疗因 I/R 损伤引起的疾病,如视网膜微循环恶化。该研究的价值在于,I/R 损伤对视网膜病变的严重程度有重要影响。然而,目前临床上尚无针对视网膜 I/R 损伤的循证治疗方法。我们的发现表明,α-MSH 在预防 I/R 介导的病变方面可能有非常广泛的用途。