Adaptation of homeostatic ocular surface epithelium to chronic treatment with the opioid antagonist naltrexone.
Adaptation of homeostatic ocular surface epithelium to chronic treatment with the opioid antagonist naltrexone.
复制标题
稳态眼表上皮对阿片类拮抗剂纳曲酮长期治疗的适应。
DOI：
10.1097/01.ico.0000224646.66472.aa
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发表时间：
2006
期刊：
影响因子：
2.8
通讯作者：
McLaughlin,PatriciaJ
中科院分区：
文献类型：
--
作者：
Zagon,IanS;Sassani,JosephW;McLaughlin,PatriciaJ
目的：研究阿片受体拮抗剂纳洛酮（NTX）对大鼠眼表上皮细胞增殖的影响。方法：成年雄性大鼠每天2次注射NTX或溶媒，每次30 mg/kg，连续7 d。NTX给药的结果包括外周角膜上皮、利姆布斯和结膜的DNA合成（用BrdU监测）、有丝分裂（用秋水仙碱测定）、细胞层数和细胞直径、凋亡和坏死以及堆积密度。此外，运输时间从基底到表面的上皮层在周边角膜进行了评估与[3 H]胸苷作为marker.Results：DNA合成和有丝分裂在基底层的周边角膜上皮的NTX治疗的大鼠分别增加了69%和85%，从对照水平，没有任何变化的参数记录在角膜缘或结膜上皮（干细胞区域）。与对照组相比，NTX组的上皮厚度增加了8%至38%，但没有更多的细胞层。与对照值相比，在利姆布斯的基底层中，NTX处理大鼠的堆积密度增加了26%，在角膜上皮、利姆布斯和结膜的基底上层中，堆积密度增加了12%至28%。在利姆布斯和结膜的基底和基底上细胞中，暴露于NTX的大鼠角膜的上皮细胞直径低于正常。NTX处理组和对照组大鼠上皮细胞凋亡和坏死可忽略不计。在NTX组的动物外周角膜上皮细胞的过境时间缩短了63%，从控制levels.Conclusions：这些数据表明，1周的治疗与NTX不诱导增生性病变或毒性在眼表上皮细胞，有一个最小的影响干细胞增殖，并加速正常的稳态过程。局部应用NTX刺激角膜上皮伤口愈合不会导致不良后遗症，从而支持该药物在治疗眼表异常中的治疗作用。
Purpose:To determine how ocular surface epithelium adjusts to an increase in cell replication after treatment with the opioid antagonist naltrexone (NTX).Methods:Adult male rats were given twice daily injections of 30 mg/kg NTX or vehicle for 7 days. Outcomes of NTX administration included DNA synthesis (monitored with BrdU), mitosis (assayed using colchicine), number of cell layers and cell diameter, apoptosis and necrosis, and packing density for the peripheral corneal epithelium, limbus, and conjunctiva. Also, transit time from basal to surface epithelial layers in the peripheral cornea was assessed with [3 H] thymidine as a marker.Results:DNA synthesis and mitosis in the basal layer of the peripheral corneal epithelium of NTX-treated rats were increased 69% and 85%, respectively, from control levels; no changes in either parameter were recorded in the limbal or conjunctival epithelium (stem cell region). Epithelial thicknesses in the NTX group were increased by 8% to 38% from control subjects, without more cell layers. Packing density in NTX-treated rats was increased from control values by 26% in the basal layer of the limbus and by 12% to 28% in the suprabasal layers of the corneal epithelium, limbus, and conjunctiva. Epithelial cell diameters from corneas of NTX-exposed rats were subnormal in the basal and suprabasal cells of the limbus and conjunctiva. Apoptosis and necrosis were negligible in the epithelium of NTX-treated and control rats. Transit times of peripheral corneal epithelial cells of animals in the NTX group were shortened by 63% from control levels.Conclusions:These data show that a 1-week treatment with NTX does not induce proliferative pathology or toxicity in ocular surface epithelium, has a minimal effect on stem cell proliferation, and accelerates normal homeostatic processes. Topical application of NTX for stimulation of corneal epithelial wound healing results in no adverse sequelae, thereby supporting the therapeutic role for this drug in the treatment of ocular surface abnormalities.