Zagon I S, Sassani J W, McLaughlin P J
Department of Neuroscience and Anatomy, The Pennsylvania State University, College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Brain Res. 1998 Aug 24;803(1-2):61-8. doi: 10.1016/s0006-8993(98)00610-6.
An endogenous opioid peptide, [Met5]-enkephalin, termed opioid growth factor (OGF) is a tonically active, autocrine-produced inhibitory molecule related to developing, neoplastic, renewing and healing tissues. The present investigation was designed to examine the role of OGF on corneal epithelial wound closure in the rabbit under in vitro and in vivo conditions. A 10-mm diameter epithelial defect was made in the center of the rabbit cornea, and the size of the defect, number of specimens with complete re-epithelialization, and rate of wound closure were evaluated using topical fluorescein and morphometric analysis. In organ culture, the influence of a complete opioid receptor blockade by naltrexone (NTX) showed an acceleration in re-epithelialization compared to controls. The action of excessive agonist (OGF) application revealed that exposure of wounded epithelium to OGF delayed wound closure under in vitro conditions, and did so in a receptor-mediated fashion. The modulatory capability of opioids on wound healing in vivo was explored by examining the effects of opioid peptide-receptor disruption using topical application of NTX, and enhanced healing of the abraded rabbit cornea was noted. The presence and location of OGF and the zeta (zeta) receptor in the normal and injured rabbit corneal epithelium were ascertained by immunocytochemistry, and both OGF and the zeta receptor were detected in basal and suprabasal epithelial cells. These results show that an opioid peptide, OGF, plays a direct role in the repair of injury to the corneal epithelium in the rabbit and acts as a receptor-mediated and constitutively expressed inhibitory molecule.
一种内源性阿片肽，[Met5]-脑啡肽，被称为阿片生长因子（OGF），是一种与发育、肿瘤、再生和愈合组织相关的具有张力活性的自分泌产生的抑制分子。本研究旨在探讨OGF在体外和体内条件下对兔角膜上皮伤口闭合的作用。在兔角膜中央制造一个直径10毫米的上皮缺损，并使用局部荧光素和形态计量分析评估缺损大小、完全重新上皮化的标本数量和伤口闭合率。在器官培养中，与对照组相比，纳曲酮（NTX）完全阻断阿片受体的影响显示重新上皮化加速。过量激动剂（OGF）应用的作用表明，在体外条件下，受伤上皮暴露于OGF会延迟伤口闭合，并且是以受体介导的方式进行的。通过局部应用NTX检查阿片肽受体破坏的影响，探索了阿片类药物在体内对伤口愈合的调节能力，并注意到兔角膜擦伤后愈合增强。通过免疫细胞化学确定正常和受伤兔角膜上皮中OGF和ζ受体的存在和位置，在基底和基底上层上皮细胞中均检测到OGF和ζ受体。这些结果表明，阿片肽OGF在兔角膜上皮损伤修复中起直接作用，并作为一种受体介导且组成性表达的抑制分子发挥作用。
