N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone reduces severity of experimental spinal cord injury
N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone reduces severity of experimental spinal cord injury
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DOI：
10.1097/01.shk.0000239775.41022.54
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发表时间：
2007-03-01
期刊：
影响因子：
3.1
通讯作者：
Cuzzocrea, Salvatore
中科院分区：
文献类型：
--
作者：
Genovese, Tiziana;Mazzon, Emanuela;Cuzzocrea, Salvatore
本研究的目的是研究N-苄氧羰基-Val-Ala-Asp-fluoromethylketones（z-VAD-fetoxone）对通过四个节段T5-T8椎板切除术将血管夹（力为24 g）应用于硬脑膜而诱导的实验性脊髓损伤程度的影响。小鼠脊髓损伤导致严重创伤，其特征在于水肿、中性粒细胞浸润、一系列炎症介质的产生、组织损伤和细胞凋亡。用有效的广泛特异性半胱天冬酶抑制剂z-VAD-favour治疗小鼠，显著降低了（1）脊髓炎症和组织损伤（组织学评分），（2）中性粒细胞浸润（髓过氧化物酶活性），（3）硝基酪氨酸形成和（4）细胞凋亡（TUNEL染色和Bax和Bcl-2表达）的程度。在一组单独的实验中，z-VAD-fatal显著改善了肢体功能的恢复（通过运动恢复评分评估）。综上所述，我们的结果清楚地表明，用z-VAD-favorite治疗减少了与脊髓创伤相关的炎症和组织损伤的发展。
The aim of this study was to investigate the effects of N-benzyloxycarbonyl-Val-Ala-Asp-fIuoromethylketones (z-VAD-fmk) on the degree of experimental spinal cord trauma induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. Spinal cord injury in mice resulted in severe trauma characterized by edema, neutrophil infiltration, production of a range of inflammatory mediators, tissue damage, and apoptosis. Treatment of the mice with z-VAD-fmk, a potent broad specific caspase inhibitor, significantly reduced the degree of (1) spinal cord inflammation and tissue injury (histological score), (2) neutrophil infiltration (myeloperoxidase activity), (3) nitrotyrosine formation, and (4),apoptosis (TUNEL staining and Bax and Bcl-2 expression). In a separate set of experiments, z-VAD-fmk significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with z-VAD-fmk reduces the development of inflammation and tissue injury associated with spinal cord trauma.