Chikawa T, Ikata T, Katoh S, Hamada Y, Kogure K, Fukuzawa K
Department of Orthopedic Surgery, School of Medicine, the University of Tokushima, Japan.
J Neurotrauma. 2001 Jan;18(1):93-103. doi: 10.1089/089771501750055802.
The effects of lecithinized superoxide dismutase (PC-SOD) and/or methylpredisolone (MP) in preventing secondary pathological changes after spinal cord injury (SCI) were investigated in rats with reference to recovery of hindlimb motor function and expression of mRNA of pro-inflammatory and neurotrophic genes. Hindlimb motor function was assessed as the BBB open field locomotor scores. The BBB scores of three groups treated with either PC-SOD (40,000 units/kg), MP (30 mg/kg), or a combination of PC-SOD and MP (PC-SOD+MP) increased with time until 3 days after SCI, and were significantly higher than that of the control group (p < 0.05). Thereafter, the score of the PC-SOD group increased, whereas that of the MP group showed a temporary decrease from day 3 to 5 and then it gradually recovered. The scores in all groups reached a plateau about 18 days after SCI. The PC-SOD+MP group did not show a synergism but a tendency similar to that of the MP group. PC-SOD and MP had down-regulatory effects on mRNA expression of pro-inflammatory substances such as interleukin-1beta (IL-1beta), intercellular adhesion molecule-1 (ICAM-1), and inducible-nitric oxide synthetase (i-NOS) after spinal cord compression at 3, 6, and 24 h, respectively, as judged by a semiquantitative reverse transcription-polymerase chain reaction and on the lipid peroxide (LPO) level 1 h after injury as determined by thiobarbituric acid-reactive substances. The suppression of pro-inflammatory genes expression, especially IL-1beta were greater in the MP group than in the PC-SOD group, while suppression of LPO level was similar in these two groups. PC-SOD+MP treatment augmented the suppression of all three pro-inflammatory genes expression and the decrease of the LPO level. The level of neurotrophin-3 (NT-3) mRNA increased from 6 h after SCI and reached a maximum after 48 h. NT-3 mRNA level was enhanced by PC-SOD treatment, but not by MP treatment. Thus, the effect of MP in suppressing these pro-inflammatory genes expression was more than that of PC-SOD. The difference in motor function in the early and later stage may be partially due to differences in expression of IL-1beta and NT-3 after either treatment, through an IL-1beta-dependent or NT-3-mediated repair response.
以大鼠后肢运动功能恢复以及促炎基因和神经营养基因的mRNA表达为参照，研究了卵磷脂化超氧化物歧化酶（PC-SOD）和/或甲基强的松龙（MP）对脊髓损伤（SCI）后继发性病理变化的影响。后肢运动功能通过BBB旷场运动评分进行评估。接受PC-SOD（40,000单位/千克）、MP（30毫克/千克）或PC-SOD与MP联合治疗（PC-SOD+MP）的三组大鼠的BBB评分随时间增加，直至SCI后3天，且显著高于对照组（p<0.05）。此后，PC-SOD组评分增加，而MP组评分在第3天至第5天出现暂时下降，随后逐渐恢复。所有组的评分在SCI后约18天达到平台期。PC-SOD+MP组未表现出协同作用，而是呈现出与MP组相似的趋势。通过半定量逆转录-聚合酶链反应判断，PC-SOD和MP分别在脊髓受压后3小时、6小时和24小时对促炎物质如白细胞介素-1β（IL-1β）、细胞间黏附分子-1（ICAM-1）和诱导型一氧化氮合酶（i-NOS）的mRNA表达具有下调作用，通过硫代巴比妥酸反应性物质测定，在损伤后1小时对脂质过氧化物（LPO）水平也有下调作用。MP组对促炎基因表达的抑制作用，尤其是对IL-1β的抑制作用大于PC-SOD组，而两组对LPO水平的抑制作用相似。PC-SOD+MP治疗增强了对所有三种促炎基因表达的抑制作用以及LPO水平的降低。神经营养因子-³（NT-³）mRNA水平从SCI后6小时开始升高，并在48小时后达到最大值。PC-SOD治疗可提高NT-³mRNA水平，但MP治疗无此作用。因此，MP对这些促炎基因表达的抑制作用大于PC-SOD。早期和后期运动功能的差异可能部分归因于两种治疗后IL-1β和NT-³表达的差异，通过IL-1β依赖性或NT-³介导的修复反应实现。
