Protective effects against the cerebral and spinal cord injury secondary to ischemia and reperfusion by inhibition of iron-dependent lipid peroxidation

胸降段或胸腹主动脉疾病手术修复后的脊髓损伤仍然是一个长期存在的临床问题。2l-氨基类固醇(拉扎类)已证明通过抑制脂质过氧化而对脑化学损伤具有保护作用。血管内皮细胞在脑缺血再灌注损伤的发病机制中起着重要作用，但目前尚不清楚拉扎类药物是否能减轻缺血后内皮细胞的损伤。我们观察了氮卓酮是否影响脊髓化学性损伤模型中促炎和抗炎细胞因子的产生。麻醉的新西兰大白兔进行20分钟的肾下主动脉阻断(AXC)，预先静脉注射3 mg/kg氮卓酮U743 89g(L组，n=10)或等容量生理盐水(P组；n=10)。假手术组(5组，n=6)，仅暴露主动脉。白介素8、-1b、-1受体…的血浆浓度在4个时间点检测更多的拮抗剂(IL-1ra)和肿瘤坏死因子(TNF)-a。分别于治疗后24小时和48小时进行Tarlov评分、脊髓病理评估和脊髓内细胞因子水平的测定。1)血浆IL-8和-1ra水平在开放后1小时达到高峰。L组血浆IL-8、-1ra水平显著低于P组(P<0.05)。(2)血浆TnFa于开放后5min达高峰，随后下降。三组间血浆TNFa水平差异无统计学意义。3)L组脊髓IL-8水平(0.98EA 0.34 ng/g组织)低于P组(7.26EA 2.26 ng/g组织)(P<0.05)。脊髓IL-1ra和TNFa差异无统计学意义。4)L组的Tarlov评分和病理评分均好于L组。1)AXC致脊髓损伤时，Lazarid U-74389G可减少全身IL-8、IL-Ira和脊髓IL-8的产生。2)这些结果表明，拉扎利类化合物可能减轻化学性内皮细胞损伤或白细胞的激活。较少

Spinal cord injury after surgical repair of the descending thoracic or thoracoabdominal aortic disease remains a persistent clinical problem.2l-aminosteroids (lazaroids) have demonstrated the protective effect against cerebral is chemic injury through the inhibition of lipidperoxidation. In the pathogenesis of is chemia-reperfusion injury the endothelium has been shown to play an important role, but little is known about whether lazaroids reduce the postischemic endothelial cell injury. We examined whether lazaroids affected the production of proinflammatory and antiinflammatory cytokines in is chemic spinal cord injury model.Anesthetized New Zealand white rabbits underwent a 20-minute infrarenal aortic crossclamping (AXC) with pretreatment of either an intravenous 3mg/kg lazaroid U743 89G (group L ; n= 10) or the same volume saline (group P ; n=l0). Sham operation group (group 5 ; n=6) underwent only exposure of the aorta. Plasma concentrations of interleukin (IL)-8, -1b, -1 receptor … More antagonist (IL-1ra) and tumor necrosis factor (TNF)-a were measured at four time points. Functional assessment with Tarlov Score at 24 and 48 hours after pretreatment, pathological assessment of the spinal cord, and measurements of cytokine levels in the spinal cord were performed.Results. 1) Plasma IL-8 and -1ra levels peaked at 1 hour after declamping. Plasma IL-8 and -1ra levels in group L were significantly lower than those in group P (*p<0.05). 2) Plasma TNFa peaked at 5 minutes after declamping, but decreased afterwards. Plasma TNFa levels were not different among three groups. 3) Spinal IL-8 levels in group L (0.98 EA 0.34 ng/g. tissue) were lower than those in group P (7.26 EA 2.26 ng/g. tissue)(*p<0.05). Spinal IL-1ra and TNFa were not significantly different. 4) Tarlov Score and pathological assessment were better in group L.Conclusions. 1) Lazaroid U-74389G reduced the production of systemic IL-8 and -Ira and spinal IL-8 when AXC caused spinal cord injury. 2) These results indicate that lazaroids may attenuate is chemic endothelial cell injury or activation of leukocytes. Less