Preconditioning with Inhalative Carbon Monoxide Protects Rat Retinal Ganglion Cells from Ischemia/Reperfusion Injury
Preconditioning with Inhalative Carbon Monoxide Protects Rat Retinal Ganglion Cells from Ischemia/Reperfusion Injury
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DOI：
10.1167/iovs.09-4894
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发表时间：
2010-07-01
影响因子：
4.4
通讯作者：
Goebel, Ulrich
中科院分区：
文献类型：
--
作者：
Biermann, Julia;Lagreze, Wolf A.;Goebel, Ulrich
目的.视网膜缺血/再灌注（I/R）损伤损害视网膜神经元。一氧化碳（CO）因其抗炎和抗凋亡作用而受到关注。在I/R损伤前通过吸入CO对视网膜神经元进行快速预处理可减轻视网膜神经节细胞（RGCs）的炎症和凋亡。在大鼠（n = 8）的左眼上进行I/R损伤，在缺血前有或没有吸入CO预处理（250ppm）1小时。损伤后7天，在整体安装中分析荧光金预标记的RGCs的密度。进一步收获视网膜组织以分析TNF-α、HSP-70和丝裂原活化蛋白激酶（MAPK）pERK 1/2和p-p38的蛋白表达。确定转录因子NF-κ B、AP-1、CREB和HSF-1的DNA结合活性，以阐明神经保护的可能途径。I/R损伤后7天，CO预处理组RGC死亡率比接受室内空气的对照组降低52%（P <0.001）。同样，CO吸入导致caspase-3活性和TNF-α蛋白表达减弱。而CO后视网膜中HSP-70蛋白表达升高，CREB和HSF-1表达呈CO依赖性调节，p-p38 MAPK表达增强。CO快速预处理在视网膜I/R损伤中介导抗炎和抗凋亡作用，从而使其具有神经保护作用。需要进一步的研究来评估CO后处理是否可能代表对抗缺血性神经元损伤的治疗选择。（Invest Ophthalmol维斯科学。2010; 51：3784 - 3791）DOI：10.1167/iovs.09-4894
PURPOSE. Retinal ischemia/reperfusion (I/R) injury damages retinal neurons. Carbon monoxide (CO) recently attracted attention as cytoprotective because of its anti-inflammatory and antiapoptotic effects. Rapid preconditioning of retinal neurons by inhaled CO before I/R injury may reduce inflammation and apoptosis in retinal ganglion cells (RGCs).METHODS. I/R injury was performed on the left eyes of rats (n = 8) with or without inhaled CO preconditioning (250 ppm) for 1 hour before ischemia. Densities of fluorogold-prelabeled RGCs were analyzed 7 days after injury in whole-mounts. Retinal tissue was further harvested to analyze protein expression of TNF-alpha, HSP-70, and mitogen-activated protein kinases (MAPKs) pERK1/2 and p-p38. DNA-binding activities of the transcription factors NF-kappa B, AP-1, CREB, and HSF-1 were determined to elucidate a possible pathway of neuroprotection.RESULTS. Seven days after I/R injury, RGC death decreased by 52% in the CO preconditioning group compared with controls receiving room air (P < 0.001). Similarly, CO inhalation resulted in attenuated caspase-3 activity and TNF-alpha protein expression. In contrast, HSP-70 protein expression was elevated in the retina after CO. CREB and HSF-1 showed CO-dependent regulation and p-p38 MAPK.CONCLUSIONS. Rapid preconditioning with CO mediates anti-inflammatory and antiapoptotic effects in retinal I/R injury, thus making it neuroprotective. Further studies are needed to evaluate whether CO posttreatment may represent a therapeutic option counteracting ischemic neuronal injury. (Invest Ophthalmol Vis Sci. 2010;51:3784-3791) DOI:10.1167/iovs.09-4894