细胞程序性坏死（Necroptosis），一种新型的半胱天冬酶非依赖性细胞死亡形式，参与了视网膜缺血再灌注损伤模型中的神经元损伤。
Necroptosis, a novel form of caspase-independent cell death, contributes to neuronal damage in a retinal ischemia-reperfusion injury model.
机构信息
Department of Neurology, SUNY Downstate Medical Center, Brooklyn, New York, USA.
出版信息
J Neurosci Res. 2010 May 15;88(7):1569-76. doi: 10.1002/jnr.22314.
UNLABELLED
Necroptosis is programmed necrosis triggered by death receptor signaling. We investigated whether necroptosis contributes to neuronal damage and functional impairment in a model of retinal ischemia.
METHODS
Sprague-Dawley rats were subjected to raised intra-ocular pressure for 45 min and received intravitreal injections of the specific necroptosis inhibitor, Nec-1, its inactive analogue (Nec-1i) or vehicle. Seven days after ischemia, ERGs were performed and then the eyes were enucleated for histological analysis. In other animals, retinas were subjected to propodium iodide, TUNEL staining or Western Blotting and probed with anti-LC-3 antibody.
RESULTS
Retinal ischemia resulted in selective neuronal degeneration of the inner layers. Pretreatment with Nec-1 led to significant preservation in thickness and histoarchitecture of the inner retina and functional improvement compared with vehicle-treated controls. Pretreatment with Nec-1i did not provide histological or functional protection. Post-treatment with Nec-1 also significantly attenuated the ERG b-wave reduction compared with ischemic vehicle controls. Nec-1 had no effect on the number of caspase or TUNEL-labelled cells in the ischemic retina but did inhibit the induction of LC-3 II and reduced the number of PI-labelled cells after ischemia.
CONCLUSION
Necroptosis is an important mode of neuronal cell death and involves autophagy in a model of retinal ischemia.
未标记
细胞坏死是由死亡受体信号触发的程序性细胞坏死。我们研究了细胞坏死是否会导致视网膜缺血模型中的神经元损伤和功能障碍。
方法
将 Sprague-Dawley 大鼠的眼内压升高 45 分钟，并接受特定的细胞坏死抑制剂 Nec-1、其无活性类似物（Nec-1i）或载体的玻璃体腔内注射。缺血后 7 天，进行 ERG 检查，然后眼球切除进行组织学分析。在其他动物中，用碘化丙啶、TUNEL 染色或 Western Blotting 处理视网膜，并使用抗 LC-3 抗体进行探测。
结果
视网膜缺血导致内层选择性神经元变性。与载体处理的对照组相比，用 Nec-1 预处理可显著保留内视网膜的厚度和组织学结构，并改善功能。用 Nec-1i 预处理不能提供组织学或功能保护。与缺血载体对照组相比，缺血后用 Nec-1 处理也显著减轻了 ERG b 波的降低。Nec-1 对缺血视网膜中 caspase 或 TUNEL 标记细胞的数量没有影响，但可抑制 LC-3 II 的诱导，并减少缺血后 PI 标记细胞的数量。
结论
细胞坏死是视网膜缺血模型中神经元细胞死亡的一种重要方式，涉及自噬。
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