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

通过抑制铁依赖性脂质过氧化作用对缺血和再灌注继发的脑和脊髓损伤的保护作用

• 批准号: 08457338
• 负责人: YASUDA Keishu
• 金额: $ 4.22万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457338/
• 关键词: lazaroid; 21-aminosteroids; Near-Infrared Spectrophotometry; iron-dependent lipid peroxidation; thoracic aortic surgery; paraplegia; postischemic spinal cord injury; Iazaroid

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

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长期存在的临床问题，2l-氨基类固醇（Lazaroids）已被证明通过抑制脂质过氧化对脑缺血损伤具有保护作用。在缺血再灌注损伤的发病机制中，内皮细胞已被证明起着重要的作用，但关于Lazaroids是否能减轻缺血后内皮细胞的损伤却知之甚少。在新西兰白色家兔脊髓损伤模型上，观察了Lazaroids对促炎性细胞因子和炎性细胞因子产生的影响。假手术组（5组，n=6）仅暴露主动脉。白细胞介素（IL）-8、-1b、-1受体的血浆浓度 ...更多信息 在四个时间点测定拮抗剂（IL-1 ra）和肿瘤坏死因子（TNF）-α。分别于预处理后24 h和48 h进行Tarlov评分，脊髓病理学检查，并检测脊髓细胞因子水平。1)血浆IL-8和-1ra水平在开放后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TNF α在开放后5分钟达到峰值，但随后下降。三组间血浆TNF α水平无差异。3)L组脊髓IL-8水平（0.98 EA 0.34 ng/g.组织）低于P组（7.26 EA 2.26 ng/g.组织）（*p<0.05）。脊髓IL-1 ra和TNF α无显著差异。4)L组的Tarlov评分和病理学评分均优于L组。1)Lazaroid U-74389 G可减少AXC引起脊髓损伤时全身IL-8和-伊拉及脊髓IL-8的产生。2)这些结果表明，拉扎类化合物可以减轻化学内皮细胞损伤或白细胞活化。少