MCI-186 reduces oxidative cellular damage and increases DNA repair function in the rabbit spinal cord after transient ischemia.
MCI-186 reduces oxidative cellular damage and increases DNA repair function in the rabbit spinal cord after transient ischemia.
复制标题
DOI：
10.1016/j.athoracsur.2004.02.133
复制
发表时间：
2004-08
期刊：
影响因子：
--
通讯作者：
G. Takahashi;M. Sakurai;K. Abe;Y. Itoyama;K. Tabayashi
中科院分区：
文献类型：
--
作者：
G. Takahashi;M. Sakurai;K. Abe;Y. Itoyama;K. Tabayashi
截瘫是胸主动脉和胸腹主动脉手术的严重并发症。为了研究这些手术中运动神经元受损的机制，我们报道了一种兔脊髓缺血模型。我们还测试了是否自由基清除剂MCI-186，这是有用的治疗缺血性损伤的大脑可以防止缺血性脊髓damage. METHODS缺血15分钟，然后MCI-186或车辆静脉注射。通过观察下肢功能和计算运动神经元数量来分析细胞损伤。为了探讨MCI-186预防缺血性脊髓损伤的机制，我们观察了作为DNA氧化损伤标志物的8-羟基-2 '-脱氧鸟苷和作为DNA修复标志物的氧化还原效应物的免疫反应性。溶剂注射组（I组）在再灌注后1d和2d观察到8-羟基-2 '-脱氧鸟苷在核内的表达。短暂缺血后8h和1d可见氧化还原效应细胞核表达，2d时表达消失。MCI-186注射组（M组）细胞核内未见8-羟基-2 '-脱氧鸟苷的表达，在缺血后8 h、1 d和2 d观察到氧化还原效应。MCI-186作为自由基清除剂，减少氧化性DNA损伤，因此氧化还原效应物没有消失。MCI-186可能是一个强有力的候选人作为一种治疗剂在治疗缺血性脊髓损伤的用途。
BACKGROUNDParaplegia is a serious complication of operations on the thoracic and thoracoabdominal aorta. To investigate the mechanism by which motor neurons are damaged during these operations, we have reported a rabbit model of spinal cord ischemia. We also tested whether a free radical scavenger MCI-186 that is useful for treating ischemic damage in the brain can protect against ischemic spinal cord damage.METHODSFifteen minutes of ischemia was induced, then MCI-186 or vehicle was injected intravenously. Cell damage was analyzed by observing the function of the lower limbs and by counting the number of motor neurons. To investigate the mechanism by which MCI-186 prevents ischemic spinal cord damage, we observed the immunoreactivity of 8-hydroxy-2'-deoxyguanosine as an oxidative DNA damage marker and redox effector as a DNA repair marker.RESULTSIn sham control, 8-hydroxy-2'-deoxyguanosine was not observed, and the nuclear expression of redox effector was observed. In vehicle injection group (group I), the nuclear expression of 8-hydroxy-2'-deoxyguanosine was observed at 1 and 2 days after reperfusion. The nuclear expression of redox effector was observed at 8 hours and 1 day, and disappeared at 2 days after transient ischemia. In MCI-186 injection group (group M), the nuclear expression of 8-hydroxy-2'-deoxyguanosine was not observed, and redox effector was observed at 8 hours and 1 and 2 days.CONCLUSIONSThese results suggest that redox effector decreased in motor neurons after transient ischemia and this reduction preceded oxidative DNA damage. MCI-186 works as a radical scavenger and reduced oxidative DNA damage, so redox effector did not disappear. MCI-186 could be a strong candidate for a use as a therapeutic agent in the treatment of ischemic spinal cord injury.