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

胸降主动脉或胸腹主动脉疾病手术修复后的脊髓损伤仍然是一个持续存在的临床问题。21 -氨基类固醇（lazaroid）通过抑制脂质过氧化作用，对脑化学损伤具有保护作用。在其化学-再灌注损伤的发病机制中，内皮细胞已被证明起重要作用，但关于类lazarids是否能减轻缺血后内皮细胞损伤的研究却很少。在化学性脊髓损伤模型中，我们检测了类虫是否影响促炎和抗炎细胞因子的产生。麻醉后的新西兰大白兔进行20分钟的肾下主动脉交叉夹夹（AXC），预处理静脉注射3mg/kg类lazaroid U743 89G （L组，n= 10）或等量生理盐水（P组，n= 10）。假手术组（5组，n=6）只显露主动脉。测定4个时间点血浆白细胞介素(IL)-8、-1b、-1受体和-1受体拮抗剂（IL-1ra）和肿瘤坏死因子(TNF)-a的浓度。预处理后24和48小时用Tarlov评分进行功能评估，脊髓病理评估，脊髓细胞因子水平测定。1)血浆IL-8和-1ra水平在降压后1小时达到峰值。L组血浆IL-8、-1ra水平显著低于P组（* P <0.05）。2)血浆TNFa在去支后5分钟达到峰值，随后逐渐下降。三组患者血浆TNFa水平无显著差异。3) L组脊髓IL-8水平（0.98 EA 0.34 ng/g）。组织)低于P组（7.26 ng/g）。组织)(* p < 0.05)。脊髓IL-1ra、TNFa差异无统计学意义。4) l组Tarlov评分及病理评分较对照组好。1) Lazaroid U-74389G在AXC引起脊髓损伤时降低了全身IL-8、-Ira和脊髓IL-8的产生。2)这些结果表明，lazaroids可能减轻化学内皮细胞损伤或白细胞活化。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