Neuroprotective effects of tempol on retinal ganglion cells in a partial optic nerve crush rat model with and without iron load
Neuroprotective effects of tempol on retinal ganglion cells in a partial optic nerve crush rat model with and without iron load
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DOI：
10.1016/j.exer.2009.10.013
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发表时间：
2010-02-01
影响因子：
3.4
通讯作者：
Schuettauf, Frank
中科院分区：
文献类型：
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作者：
Thaler, Sebastian;Fiedorowicz, Michal;Schuettauf, Frank
铁过载会导致许多组织的氧化应激。我们在相同的实验范式中研究了右旋糖酐铁预处理对校准的部分视神经挤压 (PONC) 模型中大鼠 RGC 损失的影响，以及 tempol（4-羟基-2,2,6,6-四甲基哌啶基-1-氧基，一种膜渗透性超氧化物歧化酶模拟物和自由基清除剂）提供的保护作用。总共 40 只大鼠，分为 6 组，每组 5-8 只，每组一只眼睛接受 PONC，另一只眼睛接受假挤压。在 PONC 前 24 小时对动物进行单次右旋糖酐铁负荷预处理，并在 PONC 前 6 小时用 tempol 治疗，然后在 PONC 后每天一次。对照动物用PBS处理。 RGC用荧光标记逆行标记；所有数据均以相应假治疗眼中 RGC 计数的百分比表示。进行免疫组织化学观察 3-硝基酪氨酸（硝基氧化应激的标记物）。未经铁预处理的 PONC 导致标记的 RGC 在 7 天后仅存活 31.4%。经过铁预处理的 PONC 后，存活的 RGC 甚至更少 (12.7%)。然而，当如上所述给予时，20mg/kg体重(BW)剂量的tempo显着减弱了这种作用；在没有铁预处理的组中，存活的 RGC 数量翻了一番，从 31.4% 增加到 62.1%。在铁剂预处理组中，RGC 的存活率增加得更明显，从没有 tempol 的 12.7% 增加到使用 tempol 的 46.2%。 1mg/kg BW和5mg/kg BW剂量的Tempol未显示出对RGC的显着拯救。免疫染色显示 PONC 中存在硝基酪氨酸阳性 RGC，但假手术处理的眼睛中没有，并且铁负荷后阳性细胞有所增加。 Tempol 治疗减少了铁组和非铁组的硝基酪氨酸染色。我们的结果表明，当进行铁预处理时，PONC 会导致显着更大的 RGC 损伤，并且在有或没有事先铁治疗的神经元损伤的情况下，复合 tempol 可以为 RGC 提供额外的保护。 (C) 2009 Elsevier Ltd. 保留所有权利。
Iron overload can contribute to oxidative stress in many tissues. We studied the effects of pretreatment with iron dextran on RGC loss in a calibrated partial optic nerve crush (PONC) model in rats, along with the protection offered by tempol (4-hydroxy-2,2,6,6-tetramethylpiperidinyl-1-oxyl, a membrane-permeable superoxide dismutase mimetic and free-radical scavenger), in the same experimental paradigm. A total of 40 rats in 6 groups of 5-8 animals each underwent PONC in one eye and sham crush in the other. Animals were pretreated with a single iron dextran load 24 h prior to PONC, and treated with tempol 6 h before and then once daily after PONC. Control animals were treated with PBS. RGC were retrogradely labeled with a fluorescent marker; all data are expressed in percent of the RGC count in the respective sham-treated eye. Immunohistochemistry was performed to visualize 3-nitrotyrosine, a marker of nitroxidative stress. PONC without iron pretreatment resulted in the survival of only 31.4% of labeled RGC after 7 days. Even fewer RGC (12.7%) survived after PONC with iron pretreatment. However, tempo] in doses of 20 mg/kg of body weight (BW) significantly attenuated this effect when given as described above; in the group without iron pretreatment the number of surviving RGC doubled from 31.4% to 62.1%. In the group with iron pretreatment the survival rate of RGC increased even more pronouncedly, from 12.7% without tempol to 46.2% with tempol. Tempol in doses of I mg/kg BW and 5 mg/kg BW showed no significant rescue of RGC. Immunostaining showed nitrotyrosine-positive RGCs in PONC but not in sham-treated eyes and an increase in positive cells after iron load. Tempol treatment reduced nitrotyrosine staining in both the iron and non-iron groups. Our results demonstrate that PONC results in significantly greater RGC damage when iron pretreatment is performed, and that the compound tempol may provide additional protection for RGC in cases of neuronal damage both with and without prior iron treatment. (C) 2009 Elsevier Ltd. All rights reserved.