Role of lipid peroxidation in post-traumatic spinal cord degeneration: a review.
Role of lipid peroxidation in post-traumatic spinal cord degeneration: a review.
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脂质过氧化在创伤后脊髓变性中的作用：综述。
DOI：
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发表时间：
1986
期刊：
影响因子：
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通讯作者：
J. Braughler
中科院分区：
文献类型：
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作者：
E. Hall;J. Braughler
大量的生物化学、生理学和药理学数据支持氧自由基诱导的脂质过氧化（LP）在创伤后脊髓变性中的机制作用。损伤脊髓中发生的早期和进行性脂质过氧化反应的生化证据包括：多不饱和脂肪酸过氧化产物的增加（例如，丙二醛），胆固醇的降低和胆固醇氧化产物的出现，环GMP的增加（推测是由于鸟苷酸环化酶的自由基活化），组织抗氧化剂水平的降低（例如，α-生育酚、还原型抗坏血酸盐）和抑制膜结合酶如Na ++ K +-ATP酶。体外CNS组织研究支持LP可能导致其他早期创伤后事件的可能性，包括细胞内钙积聚和花生四烯酸释放。此外，损伤后早期发生的脊髓组织乳酸酸中毒可加重LP反应。从使用已知LP抑制剂的猫的药理学研究中强烈推断LP参与了进行性创伤后脊髓白色缺血的发展。例如，糖皮质激素甲基强的松龙（MP）抑制创伤后LP和延缓缺血发展的能力的剂量-反应曲线是相同的。LP和创伤后缺血之间的这种关系更直接地从显示用高剂量抗氧化剂（例如，d-α生育酚加硒口服或1-抗坏血酸i.v.）也可以显著对抗严重钝性损伤后脊髓血流量的进行性减少。然而，某些钙和前列腺素拮抗剂的类似疗效表明，在创伤后缺血现象中，异常钙流、血管收缩剂/血小板聚集性前列腺素类和LP之间存在相互关系。除了LP在缺血发展中的作用外，强化d-α生育酚和硒预处理延缓神经节段后顺行猫运动神经纤维变性的作用表明LP也可能是神经损伤后"沃勒氏"轴突变性的基本机制。最后，LP在中枢神经系统损伤的急性病理生理学中的关键作用得到了以下发现的支持：糖皮质激素和非糖皮质激素类固醇在体外抑制神经组织LP和促进严重脑损伤小鼠的早期神经恢复的作用之间在功效和效力方面具有良好的相关性。
A large amount of biochemical, physiological, and pharmacological data has been obtained which supports a mechanistic role of oxygen free radical-induced lipid peroxidation (LP) in post-traumatic spinal cord degeneration. Biochemical evidence of early and progressive lipid peroxidative reactions occurring in the injured spinal cord includes: an increase in polyunsaturated fatty acid peroxidation products (e.g., malonyldialdehyde), a decrease in cholesterol and the appearance of cholesterol oxidation products, an increase in cyclic GMP presumably due to free radical activation of guanylate cyclase, a decrease in tissue anti-oxidant levels (e.g., alpha tocopherol, reduced ascorbate), and inhibition of membrane-bound enzymes such as Na+ + K+-ATPase. In vitro CNS tissue studies have provided support for the possibility that LP may contribute to other early post-traumatic events including intracellular calcium accumulation and arachidonic acid release. Moreover, spinal tissue lactic acidosis, which occurs early after injury, can exacerbate LP reactions. The involvement of LP in the development of progressive post-traumatic spinal white matter ischemia has been strongly inferred from pharmacological studies in cats with known inhibitors of LP. For example, the dose-response curves for the ability of the glucocorticoid methylprednisolone (MP) to inhibit post-traumatic LP and to retard ischemia development are identical. This relationship between LP and post-traumatic ischemia is more directly implied from studies showing that pretreatment of cats with high doses of anti-oxidants (e.g., d-alpha tocopherol plus selenium p.o. or 1-ascorbic acid i.v.) can also significantly antagonize the progressive decrease in spinal cord blood flow that follows severe blunt injury. However, a similar efficacy of certain calcium and prostaglandin antagonists suggests an interrelationship between aberrant calcium fluxes, vasoconstrictor/platelet aggregating prostanoids, and LP in the post-traumatic ischemic phenomenon. In addition to a role of LP in ischemia development, the action of intensive d-alpha tocopherol and selenium pretreatment to retard anterograde cat motor nerve fiber degeneration after nerve section suggests that LP may also be a fundamental mechanism of "Wallerian" axonal degeneration after neural injury. Finally, a critical role of LP in the acute pathophysiology of CNS injury in general has been supported by the finding of an excellent correlation, in terms of efficacy and potency, between the action of glucocorticoid and nonglucocorticoid steroids to inhibit neural tissue LP in vitro and to promote early neurological recovery in severely head-injured mice.
影响因子：
4.1
作者：
Wise Young;Eugene S. Flamm
通讯作者：
Wise Young;Eugene S. Flamm