Reduction of Spinal Cord Ischemia/Reperfusion Injury with Simvastatin in Rats
Reduction of Spinal Cord Ischemia/Reperfusion Injury with Simvastatin in Rats
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DOI：
10.1213/ane.0b013e318224ac35
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发表时间：
2011-09-01
影响因子：
5.7
通讯作者：
Hayashi, Jun-ichi
中科院分区：
文献类型：
--
作者：
Saito, Takeshi;Tsuchida, Masanori;Hayashi, Jun-ichi
背景：胸主动脉或胸腹主动脉的手术可能导致脊髓缺血和随后的截瘫。然而，预防脊髓缺血所致截瘫的传统策略提供的保护不足，并造成额外的副作用。在大鼠脊髓缺血/再灌注模型中，我们推测辛伐他汀具有神经保护作用。方法：将大鼠随机分为辛伐他汀组、赋形剂组和假手术组(Sham)，每组6只。动脉球囊阻断前皮下注射辛伐他汀(10 mg/kg)或赋形剂，每日1次，连续7天，再灌注后24小时皮下注射1次。用2F Fogarty导管在胸主动脉球囊扩张诱导脊髓缺血，近端平均动脉压维持在40 mm Hg12分钟。假手术组在不充气的情况下接受同样的手术。结果：辛伐他汀组再灌注后24和48h的运动缺陷指数评分均明显优于赋形剂组(P=0.021和P=0.023)。此外，辛伐他汀组的正常运动神经元数量明显多于赋形剂组(P=0.037)。辛伐他汀组白质空泡化面积百分比明显小于赋形剂组(P=0.030)。结论：辛伐他汀治疗可减轻大鼠脊髓缺血再灌注损伤后的后肢运动功能障碍和组织病理学改变。(Anesth Analg 2011；113：565-71)
BACKGROUND: Surgery of the thoracic or thoracoabdominal aorta may cause spinal cord ischemia and subsequent paraplegia. However, conventional strategies for preventing paraplegia due to spinal cord ischemia provide insufficient protection and cause additional side effects. We hypothesized that simvastatin, a drug recently shown to be neuroprotective against brain ischemia/reperfusion, would be neuroprotective in a rat spinal cord ischemia/reperfusion model.METHODS: Rats were randomly assigned to simvastatin, vehicle, or sham-surgery (sham) groups (n = 6 per group). Simvastatin (10 mg/kg) or vehicle was administered subcutaneously once daily for 7 days before aortic balloon occlusion, and once at 24 hours after reperfusion. Spinal cord ischemia was induced by balloon inflation of a 2F Fogarty catheter in the thoracic aorta, and the proximal mean arterial blood pressure was maintained at 40 mm Hg for 12 minutes. The sham group received the same operation without inflation of the balloon. Ischemic injury was assessed by hindlimb motor function using the Motor Deficit Index score at 6 to 48 hours after ischemic reperfusion, and histological assessment of the spinal cord was performed 48 hours after reperfusion.RESULTS: The Motor Deficit Index scores at 24 and 48 hours after reperfusion were significantly improved in the simvastatin group compared with the vehicle group (P = 0.021 and P = 0.023, respectively). Furthermore, there were significantly more normal motor neurons in the simvastatin group than in the vehicle group (P = 0.037). The percentage area of white matter vacuolation was significantly smaller in the simvastatin group than in the vehicle group (P = 0.030).CONCLUSIONS: Simvastatin treatment can attenuate hindlimb motor dysfunction and histopathological changes in spinal cord ischemia/reperfusion injury in rats. (Anesth Analg 2011; 113: 565-71)