Zagon I S, Sassani J W, McLaughlin P J
Departments of Neuroscience and Anatomy, The Pennsylvania State University, College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Brain Res. 1998 Jul 6;798(1-2):254-60. doi: 10.1016/s0006-8993(98)00427-2.
A native opioid peptide, [Met5]-enkephalin, termed opioid growth factor (OGF), serves as a constitutively expressed and autocrine produced inhibitory molecule related to developing, neoplastic, renewing, and healing tissues. The present study was designed to examine the effects of interfering with opioid-receptor interaction during re-epithelialization of the cornea in the rat using both systemic injections and topical applications of the potent opioid antagonist naltrexone (NTX). A 4 mm diameter epithelial defect was made in the center of the rat cornea. NTX injected twice daily or applied as eyedrops four times daily significantly accelerated re-epithelialization compared to controls. Beginning as early as 8 h after wounding, both the systemic and topical NTX treatment groups had defects that were approximately 10% to 67% smaller than control abrasions at the time points examined. Similarly, the rate of healing for the NTX groups was 4.7- and 2.8-fold greater than controls for systemic and topical paradigms, respectively. The incidence of complete re-epithelialization in animals given systemic administration of NTX was markedly accelerated in comparison to control rats; however, differences in incidence of repair between NTX and control groups receiving topical application were not observed. These results show that native opioid peptides function in wound healing, and exert a tonically inhibitory influence at the receptor level on repair of corneal epithelial injuries.
一种天然阿片肽，[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组成性表达且自分泌产生的抑制性分子。本研究旨在通过全身注射和局部应用强效阿片拮抗剂纳曲酮（NTX）来检测干扰大鼠角膜再上皮化过程中阿片受体相互作用的影响。在大鼠角膜中央制造一个直径4毫米的上皮缺损。与对照组相比，每天注射两次NTX或每天滴眼四次NTX可显著加速再上皮化。早在受伤后8小时，全身和局部NTX治疗组的缺损在检查时间点比对照擦伤小约10%至67%。同样，NTX组的愈合速度分别比全身和局部给药模式下的对照组快4.7倍和2.8倍。与对照大鼠相比，全身给予NTX的动物完全再上皮化的发生率明显加快；然而，未观察到接受局部应用的NTX组和对照组之间修复发生率的差异。这些结果表明，天然阿片肽在伤口愈合中起作用，并在受体水平对角膜上皮损伤的修复发挥持续的抑制作用。
