Yamamoto M, Ohira A, Honda O, Sato N, Furuke K, Yodoi J, Honda Y
Department of Ophthalmology, Faculty of Medicine, Kyoto University, Japan.
J Histochem Cytochem. 1997 Jan;45(1):63-70. doi: 10.1177/002215549704500109.
Prostaglandin E1 (PGE1) is commonly used in therapy for obstructive diseases, including ischemic retinopathy, in which pathogenetic reactive oxygen intermediates are responsible. However, the mechanism(s) of PGE1 in reducing tissue damage is still unclear. Adult T-cell leukemia-derived factor/human thioredoxin (ADF) is induced by oxidative stresses and has protective activity against oxidative cellular injury. To evaluate the possible involvement of ADF in the tissue-protective effect of PGE1, we analyzed ADF expression immunohistochemically using a rat transient retinal ischemia model. Rats were treated orally with 300 micrograms/kg/day OP-1206 alpha-cyclodextrin clathrate (OP-1206), a stable PGE1 analogue, for 14 days after photodynamic retinal vascular thrombosis by rose Bengal. Rats without any OP-1206 treatment were used as controls. In the OP-1206-treated rats, minimal retinal atrophy due to ischemia/reperfusion was observed histologically up to 14 days, whereas in the non-treated rats the inner layer of the retina became markedly atrophic. In parallel with the histological change, after 14 days following thrombosis ADF immunoreactivity was preserved on retinal pigment epithelial cells in the OP-1206-treated rats, whereas it was diminished in the non-treated rats. These findings suggest an important role for ADF in the OP-1206-dependent suppression of retinal tissue damage caused by oxidative insult.
前列腺素E1(PGE1)常用于治疗包括缺血性视网膜病变在内的阻塞性疾病,其中致病性活性氧中间体起作用。然而,PGE1减轻组织损伤的机制仍不清楚。成人T细胞白血病衍生因子/人硫氧还蛋白(ADF)由氧化应激诱导产生,对氧化细胞损伤具有保护活性。为了评估ADF是否可能参与PGE1的组织保护作用,我们使用大鼠短暂性视网膜缺血模型进行免疫组织化学分析ADF的表达。在用孟加拉玫瑰红进行光动力视网膜血管血栓形成后,给大鼠口服300微克/千克/天的OP-1206α-环糊精包合物(OP-1206),一种稳定的PGE1类似物,持续14天。未接受任何OP-1206治疗的大鼠用作对照。在接受OP-1206治疗的大鼠中,直至14天组织学上观察到因缺血/再灌注导致的最小程度的视网膜萎缩,而在未治疗的大鼠中,视网膜内层明显萎缩。与组织学变化平行,血栓形成后14天,接受OP-1206治疗的大鼠视网膜色素上皮细胞上的ADF免疫反应性得以保留,而在未治疗的大鼠中则减弱。这些发现表明ADF在OP-1206依赖的抑制氧化损伤引起的视网膜组织损伤中起重要作用。