Lack of protective effect of local administration of triamcinolone or systemic treatment with methylprednisolone against damages caused by optic nerve crush in rats
Lack of protective effect of local administration of triamcinolone or systemic treatment with methylprednisolone against damages caused by optic nerve crush in rats
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DOI：
10.1016/j.exer.2010.12.008
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发表时间：
2011-02-01
影响因子：
3.4
通讯作者：
Tsai, Rong Kung
中科院分区：
文献类型：
--
作者：
Huang, Tzu Lun;Chang, Chung Hsing;Tsai, Rong Kung
本研究的目的是研究曲安奈德和全身甲泼尼龙琥珀酸钠给药对视神经（ON）和视网膜神经节细胞（RGC）在大鼠模型的视神经挤压的影响。实验组在挤压实验后立即给予曲安奈德（0.5mg/条）或甲基强的松龙（MP），对照组在挤压实验后给予磷酸盐缓冲液（PBS）腹腔注射。荧光金逆行标记法计数视网膜神经节细胞密度，闪光视觉诱发电位法评估视功能。采用原位末端标记（TUNEL）法、蛋白质印迹法（Western blot）检测丝氨酸/苏氨酸激酶（p-Akt）、细胞外信号调节激酶（p-ERK）、信号转导和转录激活因子3（p-STAT 3）的表达，免疫组化法检测视神经巨噬细胞/小胶质细胞标志物ED 1的表达。视神经挤压实验后2周和4周，与相应的视神经挤压和PBS治疗的大鼠相比，曲安奈德和甲基强的松龙治疗均未挽救中央和中周边视网膜中的RGC死亡。两周后，视觉诱发电位测量显示所有治疗组的P-1波潜伏期延长（曲安奈德治疗组：123 +/- 23 ms，甲基强的松龙治疗组：133 +/- 25 ms和PBS治疗组：151 +/- 55 ms）。TUNEL检测表明，有没有减少在RGC层的曲安西龙治疗和甲基强的松龙治疗的视网膜凋亡细胞。Western blot分析显示，p-AKT，p-ERK和p-Stat 3在曲安奈德或甲基强的松龙治疗的大鼠的视网膜中均未上调。此外，任一治疗组ON病变部位的ED 1阳性细胞数量均未减少。基于这些结果，我们得出结论，无论是球后给药的曲安奈德，也没有全身给药的甲基强的松龙有任何神经保护作用，在大鼠模型的视神经挤压。(C)2010爱思唯尔有限公司版权所有。
The purpose of the present study was to investigate the effects of administrations of triamcinolone acetonide and systemic methylprednisolone sodium succinate on optic nerves (ON) and retinal ganglion cells (RGC) in a rat model of optic nerve crush. The treated groups either received triamcinolone immediately in the form of two pieces of soaked-gelform surrounding retrobulbar optic nerves (0.5 mg/per gelform) or methylprednisolone via peritoneal injection, and control group received intra-peritoneal injection with phosphate-buffered saline (PBS) after crush experiments. RGC density was counted by retrograde labeling with Fluorogold, and visual function was assessed by flash visual-evoked potentials. Terminal transferase dUTP nick end-labeling (TUNEL) assays, Western blot analysis of serine/threonine kinase (p-Akt), extracellular signal-regulated kinases (p-ERK) and signal transducer and activator of transcription 3 (p-STAT3) and immunohistochemistry of ED1, marker of macrophage/microglia in the optic nerve were conducted. Two and four weeks after optic nerve crush experiments, neither triamcinolone nor methylprednisolone treatment rescued the RGC from death in the central and mid-peripheral retinas compared with those of the corresponding optic nerve-crushed and PBS-treated rats. Visual-evoked potentials measurements showed a prolonged latency of the P-1 wave in all treated groups (triamcinolone-treated: 123 +/- 23 ms, methylprednisolone-treated: 133 +/- 25 ms and PBS-treated: 151 +/- 55 ms) after two weeks. TUNEL assays showed that there was no decrease in apoptotic cells in the RGC layers of both triamcinolone treated and methylprednisolone-treated retinas. Western blot analysis showed that p-AKT, p-ERK and p-Stat3 were not up-regulated in either retina of the triamcinolone or methylprednisolone treated rats. In addition, the number of ED1-positive cells was not attenuated at the lesion sites of the ON in either treatment group. Based upon these results, we conclude that neither retrobulbar administration of triamcinolone nor systemic administration of methylprednisolone has any neuroprotective effects in a rat model of optic nerve crush. (C) 2010 Elsevier Ltd. All rights reserved.