The protective effects of the proteasome inhibitor bortezomib (velcade) on ischemia-reperfusion injury in the rat retina.
The protective effects of the proteasome inhibitor bortezomib (velcade) on ischemia-reperfusion injury in the rat retina.
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DOI：
10.1371/journal.pone.0064262
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yang CH
中科院分区：
文献类型：
--
作者：
Chen FT;Yang CM;Yang CH
评价硼替佐米（Velcade）对大鼠视网膜缺血再灌注（IR）损伤的保护作用。在诱导IR损伤之前，将大鼠随机接受盐水、低剂量硼替佐米（0.05 mg/kg）或高剂量硼替佐米（0.2 mg/kg）治疗。视网膜电图（ERG）用于评估视网膜的功能变化。通过 PCR 和蛋白质印迹分析对炎症介质（iNOS、ICAM-1、MCP-1、TNF-α）、抗氧化蛋白（血红素加氧酶、硫氧还蛋白、过氧化还原蛋白）和促凋亡蛋白（p53、bax）的表达进行定量。进行免疫荧光研究以检测 iNOS、氧化标记物（硝基酪氨酸、8-OHdG、丙烯醛）、NF-κB p65 和 CD 68 的表达。用原位 TUNEL 染色标记视网膜细胞的凋亡。在平装视网膜中进行 Neu-N 染色，以评估视网膜神经节细胞的密度。 ERG显示IR损伤后b波降低，硼替佐米预处理，尤其是高剂量，减轻了功能损伤。硼替佐米以剂量依赖性方式成功降低了 IR 损伤后炎症介质、抗氧化蛋白、促凋亡蛋白和氧化标志物的升高。以类似的方式，硼替佐米治疗减少了 NF-κB p65 和 CD 68 阳性细胞。硼替佐米减弱了各层视网膜细胞的凋亡。盐水组和低剂量硼替佐米组的视网膜神经节细胞密度显着降低，但高剂量硼替佐米组没有显着变化。硼替佐米对视网膜 IR 损伤具有神经保护作用，其机制可能是通过抑制与 IR 损伤相关的 NF-κB 激活，减少视网膜炎症信号和氧化应激。
To evaluate the protective effects of bortezomib (Velcade) on ischemia-reperfusion (IR) injury in the rat retina. The rats were randomized to receive treatment with saline, low-dose bortezomib (0.05 mg/kg), or high-dose bortezomib (0.2 mg/kg) before the induction of IR injury. Electroretinography (ERG) was used to assess functional changes in the retina. The expression of inflammatory mediators (iNOS, ICAM-1, MCP-1, TNF-α), anti-oxidant proteins (heme oxygenase, thioredoxin, peroxiredoxin), and pro-apoptotic proteins (p53, bax) were quantified by PCR and western blot analysis. An immunofluorescence study was performed to detect the expression of iNOS, oxidative markers (nitrotyrosine, 8-OHdG, acrolein), NF-κB p65, and CD 68. Apoptosis of retinal cells was labeled with in situ TUNEL staining. Neu-N staining was performed in the flat-mounted retina to evaluate the density of retinal ganglion cells. ERG showed a decreased b-wave after IR injury, and pretreatment with bortezomib, especially the high dosage, reduced the functional impairment. Bortezomib successfully reduced the elevation of inflammatory mediators, anti-oxidant proteins, pro-apoptotic proteins and oxidative markers after IR insult in a dose-dependent manner. In a similar fashion, NF-κB p65- and CD 68-positive cells were decreased by bortezomib treatment. Retinal cell apoptosis in each layer was attenuated by bortezomib. The retinal ganglion cell density was markedly decreased in the saline and low-dose bortezomib groups but was not significantly changed in the high-dose bortezomib group. Bortezomib had a neuro-protective effect in retinal IR injury, possibly by inhibiting the activation of NF-κB related to IR insult and reducing the inflammatory signals and oxidative stress in the retina.
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影响因子：
4.4
作者：
Biermann, Julia;Lagreze, Wolf A.;Goebel, Ulrich
通讯作者：
Goebel, Ulrich
影响因子：
4.4
作者：
Jo, N;Wu, GS;Rao, NA
通讯作者：
Rao, NA
影响因子：
4.4
作者：
Chen, Fang-Ting;Liu, Yi-Chun;Yang, Chang-Hao
通讯作者：
Yang, Chang-Hao
DOI：
10.1097/iae.0b013e31815ec32d
发表时间：
2008-04-01
影响因子：
3.3
作者：
Gustavsson, Carin;Agardh, Carl-David;Agardh, Per Hagert Elisabet
通讯作者：
Agardh, Per Hagert Elisabet
影响因子：
3.1
作者：
HATCHELL, DL;WILSON, CA;SALOUPIS, P
通讯作者：
SALOUPIS, P