Williams A J, Berti R, Yao C, Price R A, Velarde L C, Koplovitz I, Schultz S M, Tortella F C, Dave J R
Walter Reed Army Institute of Research, Division of Neurosciences, Silver Spring, MD 20910, USA.
Neurosci Lett. 2003 Oct 9;349(3):147-50. doi: 10.1016/s0304-3940(03)00818-8.
Effective treatments to improve survivability following exposure to the nerve agent soman have been established and are currently available. Unfortunately, electrographic brain seizures, neuroinflammation and brain cell death are still a potential problem even with treatment. In the present study we have characterized the time course of the central neuro-inflammatory gene response using quantitative real time-PCR (TaqMan). Male Sprague-Dawley rats were pre-treated with HI-6 (1-2-hydroxy-iminomethyl-1-pyridino-3-(4-carbamoyl-1-pyridino-2-oxapropane dichloride); 125 mg/kg, i.p.) and exposed 30 min later to 1.6 x LD(50) of soman (pinacolyl methyl-phosphonofluoridate, 180 microg/kg, s.c.) followed at 1 min by atropine methyl nitrate (4 mg/kg, i.m.). Initially, a significant and dramatic upregulation of tumor necrosis factor-alpha and vascular cell adhesion molecule-1 mRNA levels was measured 2 h post-exposure followed at 6 h by upregulation of interleukin-1beta, interleukin-6, E-selectin, and intercellular adhesion molecule-1 with eventual resolution by 24-48 h. In conclusion, an acute and transient upregulation of the inflammatory gene response is activated following soman exposure that may be involved in the soman-induced brain injury process.
已确立并现有有效的治疗方法来提高接触神经性毒剂梭曼后的生存率。不幸的是，即使经过治疗，脑电图癫痫发作、神经炎症和脑细胞死亡仍是潜在问题。在本研究中，我们使用定量实时聚合酶链反应（TaqMan）对中枢神经炎症基因反应的时间进程进行了表征。雄性Sprague-Dawley大鼠预先接受HI-6（1-2-羟基亚氨基甲基-1-吡啶基-3-(4-氨基甲酰基-1-吡啶基-2-氧杂丙烷二氯化物)；125毫克/千克，腹腔注射）处理，30分钟后暴露于1.6倍半数致死剂量的梭曼（频那基甲基膦酰氟，180微克/千克，皮下注射），随后1分钟后给予硝酸甲基阿托品（4毫克/千克，肌肉注射）。最初，暴露后2小时测量到肿瘤坏死因子-α和血管细胞黏附分子-1 mRNA水平显著且急剧上调，6小时后白细胞介素-1β、白细胞介素-6、E-选择素和细胞间黏附分子-1上调，最终在24-48小时消退。总之，梭曼暴露后会激活炎症基因反应的急性和短暂上调，这可能参与了梭曼诱导的脑损伤过程。
