Riazi-Esfahani Mohammad, Kiumehr Saman, Asadi-Amoli Fahimeh, Lashay Ali R, Dehpour Ahmad R
Eye Research Center, School of Medicine, Tehran University of Medical Sciences, Iran.
Retina. 2008 Mar;28(3):511-7. doi: 10.1097/IAE.0b013e31815960c3.
Pharmacologic preconditioning with morphine has been shown to protect several kinds of tissues against ischemia-reperfusion injury. The aim of the present study was to investigate whether intravitreal administration of morphine induces structural protection against ischemic damage in a rabbit model of ischemic retinopathy.
Twenty-eight male white New Zealand rabbits were used. Animals in saline control group received 0.1 mL of phosphate-buffered saline (PBS) intravitreally with no postinjection ischemia. In the saline-control ischemia group, 15 minutes after injection of PBS, retinal ischemia was induced by raising intraocular pressure to 150 mmHg for 60 minutes. In three treatment-ischemia groups, morphine (1, 5, and 10 micromol/L) was administered intravitreally 15 minutes before induction of ischemia. In another experiment, naloxone (40 micromol/L) was administered 5 minutes before intravitreal administration of morphine (10 micromol/L) followed by 60 minutes of ischemia to investigate the role of opioid receptors in mediating the possible protective effect of morphine. Toxicity controls were performed with morphine (10 micromol/L) and naloxone (40 micromol/L) without ischemia. Histologic evaluation was performed for all groups on the seventh postoperative day.
Sixty minutes of ischemia led to severe cell loss in ganglion cell layer and thinning of the inner nuclear layer in saline-control ischemia compared to that of the nonischemia control group (P < 0.001). Thickness of the inner plexiform layer to the inner limiting membrane was significantly increased due to edema (P < 0.001). Administration of morphine in higher doses (5 and 10 micromol/L) significantly improved all of the above mentioned indices (P < 0.05). Administration of naloxone 15 minutes before morphine reversed most of the morphine protective effects.
Morphine pretreatment provides significant histologic protection against ischemic injury in rabbit retina. Pharmacologic evidence suggests that this protective phenomenon may be mediated in part by opiate receptors.
已证明吗啡进行药物预处理可保护多种组织免受缺血再灌注损伤。本研究的目的是调查玻璃体内注射吗啡是否能在兔缺血性视网膜病变模型中诱导对缺血损伤的结构保护作用。
使用28只雄性新西兰白兔。生理盐水对照组动物玻璃体内注射0.1 mL磷酸盐缓冲盐水（PBS），注射后无缺血处理。在生理盐水对照缺血组中，注射PBS 15分钟后，通过将眼压升高至150 mmHg持续60分钟诱导视网膜缺血。在三个治疗缺血组中，在诱导缺血前15分钟玻璃体内注射吗啡（1、5和10 μmol/L）。在另一项实验中，在玻璃体内注射吗啡（10 μmol/L）前5分钟注射纳洛酮（40 μmol/L），随后进行60分钟的缺血处理，以研究阿片受体在介导吗啡可能的保护作用中的作用。使用吗啡（10 μmol/L）和纳洛酮（40 μmol/L）进行无缺血的毒性对照。在术后第7天对所有组进行组织学评估。
与非缺血对照组相比，60分钟的缺血导致生理盐水对照缺血组神经节细胞层严重细胞丢失和内核层变薄（P < 0.001）。由于水肿，内丛状层至内界膜的厚度显著增加（P < 0.001）。高剂量（5和10 μmol/L）吗啡给药显著改善了上述所有指标（P < 0.05）。在吗啡给药前15分钟注射纳洛酮可逆转大部分吗啡的保护作用。
吗啡预处理可为兔视网膜缺血损伤提供显著的组织学保护。药理学证据表明，这种保护现象可能部分由阿片受体介导。
