Fibroblast growth factor 21 inhibits ferroptosis following spinal cord injury by regulating heme oxygenase-1

Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury.Fibroblast growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a regulator of iron and reactive oxygen species homeostasis.The relationship between heme oxygenase-1and ferroptosis remains controve rsial.In this study,we used a spinal co rd injury rat model to show that the levels of fibroblast growth factor 21 in spinal co rd tissue decreased after spinal cord injury.In addition,there was a significant aggravation of ferroptosis and a rapid increase in heme oxygenase-1 expression after spinal cord injury.Furthe r,heme oxygenase-1 aggravated fe rroptosis after spinal cord injury,while fibroblast growth factor 21 inhibited fe rroptosis by downregulating heme oxygenase-1.Thus,the activation of fibroblast growth factor 21 may provide a potential treatment for spinal co rd injury.These findings could provide a new potential mechanistic explanation for fibroblast growth factor 21 in the treatment of spinal cord injury.

Metformin alleviates spinal cord injury by inhibiting nerve cell ferroptosis through upregulation of heme oxygenase-1 expression

Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury models.Heme oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox homeostasis.Metformin is a classic drug used to treat type 2 diabetes that can inhibit ferroptosis.Previous studies have shown that,when used to treat cardiovascular and digestive system diseases,metformin can also upregulate heme oxygenase-1 expression.Therefore,we hypothesized that heme oxygenase-1 plays a significant role in mediating the beneficial effects of metformin on neuronal ferroptosis after spinal cord injury.To test this,we first performed a bioinformatics analysis based on the GEO database and found that heme oxygenase-1 was upregulated in the lesion of rats with spinal cord injury.Next,we confirmed this finding in a rat model of T9 spinal cord compression injury that exhibited spinal cord nerve cell ferroptosis.Continuous intraperitoneal injection of metformin for 14 days was found to both upregulate heme oxygenase-1 expression and reduce neuronal ferroptosis in rats with spinal cord injury.Subsequently,we used a lentivirus vector to knock down heme oxygenase-1 expression in the spinal cord,and found that this significantly reduced the effect of metformin on ferroptosis after spinal cord injury.Taken together,these findings suggest that metformin inhibits neuronal ferroptosis after spinal cord injury,and that this effect is partially dependent on upregulation of heme oxygenase-1.

Erythropoietin inhibits ferroptosis and ameliorates neurological function after spinal cord injury

Ferroptosis is one of the critical pathological events in spinal cord injury.Erythropoietin has been reported to improve the recovery of spinal cord injury.However,whether ferroptosis is involved in the neuroprotective effects of erythropoietin on spinal cord injury has not been examined.In this study,we established rat models of spinal cord injury by modified Allen’s method and intraperitoneally administered 1000 and 5000 IU/kg erythropoietin once a week for 2 successive weeks.Both low and high doses of erythropoietin promoted recovery of hindlimb function,and the high dose of erythropoietin led to better outcome.High dose of erythropoietin exhibited a stronger suppressive effect on ferroptosis relative to the low dose of erythropoietin.The effects of erythropoietin on inhibiting ferroptosis-related protein expression and restoring mitochondrial morphology were similar to those of Fer-1(a ferroptosis suppressor),and the effects of erythropoietin were largely diminished by RSL3(ferroptosis activator).In vitro experiments showed that erythropoietin inhibited RSL3-induced ferroptosis in PC12 cells and increased the expression of xCT and Gpx4.This suggests that xCT and Gpx4 are involved in the neuroprotective effects of erythropoietin on spinal cord injury.Our findings reveal the underlying anti-ferroptosis role of erythropoietin and provide a potential therapeutic strategy for treating spinal cord injury.

Mesenchymal stem cells,extracellular vesicles,and transcranial magnetic stimulation for ferroptosis after spinal cord injury

Spinal cord injury is characte rized by diffe rent aetiologies,complex pathogenesis,and diverse pathological changes.Current treatments are not ideal,and prognosis is generally poor.After spinal cord injury,neurons die due to various forms of cell death.Among them,fe rroptosis causes dysfunction after spinal cord injury,and no existing traditional treatments have been indicated to block its occurrence.Meanwhile,emerging therapies using mesenchymal stem cells,extracellular vesicles,and transcranial magnetic stimulation therapy are promising for reve rsing spinal co rd neuronal ferroptosis after spinal cord injury.However,no definitive studies have demonstrated the effectiveness of these approaches.This review summarizes the existing research on the mechanisms of ferroptosis;fe rroptosis after spinal cord injury;treatment of spinal cord injury with mesenchymal stem cells,extracellular vesicles,and transc ranial magnetic stimulation;and treatment of ferroptosis using mesenchymal stem cells,extracellular vesicles,and transc ranial magnetic stimulation.Inhibiting ferroptosis can promote the reversal of neurological dysfunction after spinal cord injury.In addition,mesenchymal stem cells,extracellular vesicles,and transc ranial magnetic stimulation can reve rse adverse outcomes of spinal cord injury and regulate ferroptosis-related fa ctors.Thus,it can be inferred that mesenchymal stem cells,extracellular vesicles,and transcranial magnetic stimulation have the potential to inhibit fe rroptosis after spinal cord injury.This review serves as a reference for future research to confirm these conclusions.

Deferoxamine promotes recovery of traumatic spinal cord injury by inhibiting ferroptosis

Ferroptosis is an iron-dependent novel cell death pathway. Deferoxamine, a ferroptosis inhibitor, has been reported to promote spinal cord injury repair. It has yet to be clarified whether ferroptosis inhibition represents the mechanism of action of Deferoxamine on spinal cord injury recovery. A rat model of Deferoxamine at thoracic 10 segment was established using a modified Allen's method. Ninety 8-week-old female Wistar rats were used. Rats in the Deferoxamine group were intraperitoneally injected with 100 mg/kg Deferoxamine 30 minutes before injury. Simultaneously, the Sham and Deferoxamine groups served as controls. Drug administration was conducted for 7 consecutive days. The results were as follows:(1) Electron microscopy revealed shrunken mitochondria in the spinal cord injury group.(2) The Basso, Beattie and Bresnahan locomotor rating score showed that recovery of the hindlimb was remarkably better in the Deferoxamine group than in the spinal cord injury group.(3) The iron concentration was lower in the Deferoxamine group than in the spinal cord injury group after injury.(4) Western blot assay revealed that, compared with the spinal cord injury group, GPX4, xCT, and glutathione expression was markedly increased in the Deferoxamine group.(5) Real-time polymerase chain reaction revealed that, compared with the Deferoxamine group, mRNA levels of ferroptosis-related genes Acyl-CoA synthetase family member 2(ACSF2) and iron-responsive element-binding protein 2(IREB2) were up-regulated in the Deferoxamine group.(6) Deferoxamine increased survival of neurons and inhibited gliosis. These findings confirm that Deferoxamine can repair spinal cord injury by inhibiting ferroptosis. Targeting ferroptosis is therefore a promising therapeutic approach for spinal cord injury.

Sodium selenite promotes neurological function recovery after spinal cord injury by inhibiting ferroptosis

Ferroptosis is a recently discovered form of iron-dependent cell death,which occurs during the pathological process of various central nervous system diseases or injuries,including secondary spinal cord injury.Selenium has been shown to promote neurological function recovery after cerebral hemorrhage by inhibiting ferroptosis.However,whether selenium can promote neurological function recovery after spinal cord injury as well as the underlying mechanism remain poorly understood.In this study,we injected sodium selenite(3μL,2.5μM)into the injury site of a rat model of T10 vertebral contusion injury 10 minutes after spinal cord injury modeling.We found that sodium selenite treatment greatly decreased iron concentration and levels of the lipid peroxidation products malondialdehyde and 4-hydroxynonenal.Furthermore,sodium selenite increased the protein and mRNA expression of specificity protein 1 and glutathione peroxidase 4,promoted the survival of neurons and oligodendrocytes,inhibited the proliferation of astrocytes,and promoted the recovery of locomotive function of rats with spinal cord injury.These findings suggest that sodium selenite can improve the locomotive function of rats with spinal cord injury possibly through the inhibition of ferroptosis via the specificity protein 1/glutathione peroxidase 4 pathway.

Changes of free iron contents and its correlation with lipid peroxidation after experimental spinal cord injury

Objective: To observe the dynamic changes of fre e iron contents and its relationship to the changes of lipid peroxidation after experimental spinal cord injury (SCI). Methods: Sprague Dawley rats were randomly divided into three g roups: Group A (n=6) received no operation; Group B (n=48) received only laminec tomy (sham); and Group C (n=48) received both laminectomy and traumatic injury ( SCI model). The SCI animal models were made by using an modified Allens weight -drop device (50 g.cm) on T_ 12 . Rats were sacrificed at 0.5 ,1,3,6,12,24 hours after injury. The levels of free iron involved in spinal cord segm ents at different time points were measured by bleomycin assay. The malondialdeh yde (MDA) was also measured by the thiobarbituric acid (TBA). Results: After SCI in Group C,the level of free iron showed a significant increase at 0.5 hour compared to Groups B and A,restored to th e control level at 6 h; the level of MDA was increased at 0.5 hour,peaked a t 3 hours,returned to the control level at 12 hours; the concentrations of free iron and lipid peroxidation in injured rats were significantly and positively c orrelated at 0.5 -3 hours. Conclusions: After SCI the levels of free iron are increased qu ickly and might be a major contributor to lipid peroxidation in injured spinal c ord.

Antioxidation of melatonin against spinal cord injury in rats

Background The iron catalyzed lipid peroxidation plays an important role in the autodestruction of the injured spinal cord. This study was to detect the antioxidation of melatonin against spinal cord injury (SCI) in rats.Methods Sity Sprague-Dawley rats were randomly divided into four groups: group A (n=15) for laminectomyanly, group B (n=15) for laminectomy with SCI, group C (n=15) for SCI and intraperitoneal injection of a bolus of 100 mg/kg melatonin, and group D (n=15) for SCI and intraperitoneal injection of saline containing 5% ethanol. The SCI of animal model was made using modified Allen’s method on T 12. Six rats of each group were sacrificed 4 hours after injury, and the levels of free iron and malondialdehyde (MDA) of the involved spinal cord segments were measured by the bleomycin assay and thiobarbituric acid (TBA) separately. Functional recovery of the spinal cord was assessed by Modified Tarlov’s scale and the inclined plane method at 1, 3, 7, 14, 21 days after SCI. The histologic changes of the damaged spinal cord were also examined at 7 days after SCI. Results After SCI, the levels of free iron and MDA were increased significantly and the modified Tarlov’s score and inclined plane angle decreased significantly in groups B and D. In group C, the Tarlov’s score and inclined plane angle were increased significantly at 7, 14 and 21 days, with histological improvement.Conclusion: Melatonin can reduce the level of lipid peroxidation and prvent damage to the spinal cord of rat.

Antioxidation of quercetin against spinal cord injury in rats

客观：在老鼠在试验性的针的绳索损害(SCI ) 上观察橡黄素的效果。方法：六十只 Sprague-Dawley 老鼠随机被划分成四个组；仅仅为 laminectomy 的组 A，为有 SCI 的 laminectomy 的组 B，为有为 SCI 和 intraperitoneal 注射的 200 mg/kg 橡黄素和组 D 的一丸大丸药的 SCI 和 intraperitonealinjection 的组 C 盐。SCI 模型被使用修改侨民做“ T_(12 ) 上的 s 方法。每个组的六只老鼠在损害和免费的铁的层次以后在 4 h 被打死，深奥针的绳索片断的 malondialdehyde (MDA ) 被 bleomycin 和 thiobarbituric 酸(TBA ) 测量试金独立。后部的手足功能的 Therecovery 被修改 Tarlov 估计“在在 SCI 以后的 7 d， 14 d 和 21 d 的 s 规模和斜面方法。损坏针的绳索的组织学的变化也在 SCI 以后在 7 d 被检验。结果：在 SCI 以后，免费的铁和 MDA 的层次显著地在组 B 和 D 被增加，当时不在组 C。修改 Tarlov “ s 分数和斜面角度显著地在组 B， C 和 D 被减少。组织学的调查结果没被改进。结论：在 SCI 以后，橡黄素能每氧化减少类脂化合物的水平，然而并非改进功能的恢复。

褪黑素对大鼠实验性脊髓损伤的神经保护作用

目的观察不同剂量褪黑素对实验性脊髓损伤(SCI)大鼠早期脂质过氧化水平及超微结构的神经保护作用。方法采用钳夹法在大鼠T10水平建立SCI模型。60只SCI模型大鼠随机分为6组:模型Ⅰ组仅行椎板切除,模型Ⅱ组行椎板切除+钳夹,对照组损伤后立即给予5%无水乙醇0.2ml,甲泼尼龙治疗组给予甲泼尼龙30mg/kg,褪黑素治疗Ⅰ组给予褪黑素50mg/kg,褪黑素治疗Ⅱ组给予褪黑素100mg/kg。于伤后24h检测各组大鼠受损部位脊髓丙二醛(MDA)含量并进行超微结构病理改变评分。结果模型Ⅰ组及各治疗组MDA含量明显低于模型Ⅱ组和对照组(P<0.05),褪黑素治疗组与甲泼尼龙治疗组间差异无统计学意义(P>0.05),两个褪黑素治疗组之间差异亦无统计学意义(P>0.05)。超微组织病理改变评分结果显示,褪黑素治疗Ⅱ组的神经保护作用与甲泼尼龙治疗组相当(P>0.05),褪黑素治疗Ⅱ组的结果优于褪黑素治疗Ⅰ组(P<0.05)。结论褪黑素可抑制实验性脊髓损伤早期脂质过氧化水平,从而发挥神经保护作用。

人参皂甙治疗脊髓损伤的实验研究

目的 探讨人参皂甙对脊髓损伤的作用 ,寻求治疗脊髓损伤的新方法。方法 采用改良 Allen氏重量打击法制作猫脊髓损伤模型。动物随机分组 ,通过生物化学及病理学手段检测急性脊髓损伤中脊髓损伤节段水、钙离子 (Ca2 + )、丙二醛 (MDA)含量 ,过氧化物歧化酶 (SOD)、谷胱苷肽过氧化物酶 (GSH)活性 ,观察伤段脊髓光境下组织形态改变及人参皂甙对其的影响。结果 1损伤组伤段脊髓水、Ca2 + 、MDA含量明显升高 ,SOD、GSH活性明显降低 (P<0 .0 )。 2光镜下各组均有水肿 ,损伤组最重、治疗组次之、对照组最轻 ;损伤组及治疗组均有中心性出血 ,损伤组较重 ;损伤组 3h即出现神经元空泡变性 ,核溶解或固缩 ,尼氏小体消失 ;6h出现部分神经纤维脱髓鞘或断裂。治疗组均有不同程度的恢复。结论 人参皂甙对脊髓损伤早期有保护作用。

淫羊藿苷可减轻大鼠脊髓损伤后的脂质过氧化

目的研究淫羊藿苷对大鼠脊髓损伤后脂质过氧化的影响。方法 72只健康成年清洁级雄性SD大鼠按随机数字表法分为淫羊藿苷组、对照组及假手术组3组,每组24只。对照组和淫羊藿苷组采用改良Allen法制作脊髓损伤模型,假手术组仅切开椎板不损伤脊髓。术后即刻淫羊藿苷组给予淫羊藿苷(100 mg/kg)灌胃,对照组和假手术组给予等量生理盐水灌胃,1次/d。术后24 h采用硫代巴比妥酸法检测丙二醛(MDA)含量,黄嘌呤氧化酶法检测超氧化物歧化酶(SOD)活性;采用干湿重法检测脊髓组织的含水量;术后48 h采用透射电镜观察脊髓组织超微结构,并采用Kaptanoglu评分法进行超微结构评分;术后7、14、21、28 d采用BBB评分法评定大鼠运动功能。结果术后24 h对照组和淫羊藿苷组MDA含量显著高于假手术组,淫羊藿苷组低于对照组,差异有统计学意义(P<0.05);对照组和淫羊藿苷组SOD活性显著低于假手术组,淫羊藿苷组高于对照组,差异有统计学意义(P<0.05)。术后48 h,对照组和淫羊藿苷组脊髓组织含水量、超微结构评分均显著高于假手术组,淫羊藿苷组均显著低于对照组(P<0.05)。术后各时间点对照组和淫羊藿苷组大鼠BBB评分均低于假手术组,差异有统计学意义(P<0.05);淫羊藿苷组大鼠BBB评分高于对照组,差异有统计学意义(P<0.05)。结论淫羊藿苷能够明显降低脊髓损伤后的MDA含量,升高SOD的活性,减轻脂质过氧化、脊髓水肿和脊髓的组织病理学损伤,改善脊髓损伤大鼠的运动功能,有效地保护脊髓组织和神经作用。

银杏叶提取物对兔脊髓缺血再灌注损伤的保护作用

目的:探讨银杏叶提取物对兔脊髓缺血再灌注(ischemiareperfusion,IR)损伤的保护作用及其机制。方法:27只新西兰大白兔随机分为假手术组、模型组和银杏叶提取物治疗组,每组9只。建立兔脊髓IR模型。对脊髓IR前及IR后24、48h实验兔后肢运动功能进行评分,检测缺血脊髓组织中超氧化物歧化酶(superoxidedismutase,SOD)和丙二醛(malondialdehyde,MDA)的含量,并检测缺血脊髓组织神经细胞的凋亡指数及Bcl2、Bax蛋白的表达水平。结果:银杏叶提取物可明显改善脊髓IR后实验兔的后肢运动功能;提高脊髓组织中SOD的活性,降低MDA的水平;通过上调Bcl2及下调Bax蛋白的表达,抑制IR所致的脊髓神经细胞的凋亡。结论:银杏叶提取物对脊髓IR损伤有一定的保护作用,其机制可能与减轻脊髓神经细胞脂质过氧化损伤和抑制神经细胞的凋亡有关。

蝮蛇抗栓酶对脊髓损伤影响的实验研究

就蝮蛇抗栓酶对大鼠脊髓损伤时脂质过氧化物、超氧化物歧化酶及组织形态学的影响作了研究。结果表明：蝮蛇抗栓酶治疗组脊髓组织和血浆中脂质过氧化物（ＬＰＯ）含量较对照组低，其脊髓组织和红细胞的超氧化物歧化酶（ＳＯＤ）活性较对照组高，光镜和电镜检查均显示治疗组大鼠的脊髓损伤比对照组轻，脊髓神经功能恢复情况亦优于对照组。表明蝮蛇抗栓酶对大鼠脊髓损伤的影响与其抗氧自由基作用有关。

TRH对大鼠脊髓损伤脂质过氧化的影响

本实验以大鼠脊髓损伤(SCI,50gcm)模型,研究TRH对SCI脂质过氧化的影响。结果表明,于SCI后立即iv不同剂量的TRH(0.2mg/kg,0.6mg/kg,2.0mg/kg,每小时1次,连续4次),可显著地抑制伤段脊髓组织脂质过氧化反应,使丙二醛(MDA)含量显著降低,并呈剂量依赖关系j;TRH还可使组织超氧化物歧化酶(SOD)活性明显升高。提示TRH抗SCI脂质过氧化反应是通过升高SOD活性,清除自由基(尤其是氧自由基)介导的,它可能是1种有效的自由基清除剂。

电针对急性脊髓损伤大鼠白细胞介素-1β表达变化的影响

目的观察电针治疗对脊髓损伤(SCI)大鼠脊髓组织白细胞介素(IL)-1β表达变化的影响,探究其与脊髓损伤后炎症反应和细胞凋亡的关系。方法选用2月龄SD大鼠80只。随机将大鼠分为对照组和电针组。采用Allen法建立大鼠急性SCI模型,用免疫组化方法检测两组大鼠脊髓神经元胞浆IL-1β及胱氨酸酶(caspase-3)变化,用比色法检测其脊髓组织匀浆超氧化物歧化酶(SOD)、丙二醛(MDA)水平,用原位末端标记法(TUNEL)检测两组大鼠脊髓神经元和胶质细胞凋亡。结果治疗结束时,与对照组相比,电针组IL-1β和caspase-3阳性细胞数明显减少(P<0.01),IL-1β和caspase-3阳性细胞的平均灰度值明显提高(P<0.01);MDA水平明显降低(P<0.01),SOD水平明显升高(P<0.01);TUNEL阳性细胞数明显减少(P<0.01)。结论电针治疗后,急性脊髓损伤大鼠脊髓IL-1β及caspase-3表达减少,减轻了脊髓损伤后炎症反应和细胞凋亡。

三七总皂甙对大鼠脊髓损伤组织总钙和脂质过氧化的影响

打击法致大鼠脊髓损伤(SCI,50gcm)4 h后脊髓组织MDA、FFA含量均显著增加(P<0.01);XOD活性显著升高(P<0.05),SOD活性显著降低(P<0.01);[Ca^(2+)]t显著增加(P<0.001)。表明SCI病理过程中伴随Ca^(2+)介导的自由基生成和膜脂质过氧化反应。不同剂量的(30、90、270mg/kg,ⅳ)PNS均可抑制MDA生成(P<0.01);大剂量(270mg/kg)PNS还可抑制FFA释放和XOD活性(P<0.05);90mg/kg PNS亦可使[Ca^(2+)]t显著降低(P<0.001)。提示PNS抑制细胞Ca^(2+)内流可能是其抗脂质过氧化反应的主要机理之一。

他克莫司抑制脂质过氧化对大鼠脊髓的保护效应观察

目的探讨大鼠脊髓损伤后早期应用他克莫司对脊髓的保护效应。方法健康成年雄性Wistar大鼠40只,随机分为他克莫司组(n=20)和损伤组(n=20)。采用Allen's法建立大鼠脊髓损伤模型,他克莫司组在脊髓损伤后5min一次性经尾静脉注射他克莫司0.3mg/kg,损伤组以相同方法给予等量生理盐水。伤后3、7、14、21d应用BBB评分法进行后肢运动功能评价,并分别采用黄嘌呤氧化酶法和硫代巴比妥酸法测定血浆超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量变化,免疫组织化学染色检测脊髓组织诱导型一氧化氮合酶(iNOS)的表达。结果与损伤组比较,他克莫司组各时间点行为学评分明显改善(P<0.05或P<0.01),血浆MDA含量降低、SOD活性升高(P<0.05或P<0.01)。损伤组和他克莫司组iNOS蛋白表达均于伤后3d升高,7d达峰值,且他克莫司组各时间点阳性细胞率均明显低于损伤组(P<0.05或P<0.01)。结论他克莫司可减少大鼠脊髓损伤后iNOS的表达和自由基生成,从而抑制脂质过氧化损伤,改善神经功能。

三七总皂甙对大鼠脊髓损伤作用的实验研究

目的:探讨三七总皂甙对脊髓损伤(SCI)的作用。方法:60只Wistar大鼠随机分为对照组、手术组和治疗组。采用改良的Allen s撞击法制作大鼠SCI模型。通过生物化学方法检测急性SCI中SCI段H2O、Ca2+、丙二醛(MDA)的含量及超氧化物歧化酶(SOD)活性,并在光镜下观察伤段脊髓组织的形态改变。结果:①治疗组伤段脊髓H2O、Ca2+、MDA含量明显低于手术组;而SOD活性较手术组明显偏高(P<0.05)。②光镜下手术组和治疗组均有水肿及中心性出血,且手术组较明显。手术组术后2 h中央管结构部分破坏,神经元变性,部分核固缩或溶解,尼氏小体淡染,术后6 h出现部分神经纤维脱髓鞘或断裂;治疗组则呈现损伤部分修复。结论:三七总皂甙对大鼠SCI早期有保护作用。

甲氨蝶呤对大鼠脊髓挫伤急性期脂质过氧化的影响

目的:观察甲氨蝶呤对大鼠脊髓挫伤后脂质过氧化的影响,探讨其急性期抗氧化神经保护机制。方法:采用PinPointTM精密皮质撞击器制备大鼠脊髓挫伤模型,伤后30 min皮下注射(subcutaneous injection,sc)甲氨蝶呤(0.5 mg·kg-1·BW),采用酶联免疫吸附法检测血浆中丙二醛(malondialdehyde,MDA)和8-异前列腺素F2α(8-iso-Prostaglandin F2α,8-iso-PGF2α)的含量以及损伤组织中4-羟基壬烯醛-His加合物(4-hydroxynonenal-His adduct,HNE)的含量。结果:伤后1、3、6、12、24、48、72 h,甲氨蝶呤组MDA、8-iso-PGF2α以及HNE的含量均低于模型组;尤其在伤后6、12 h,甲氨蝶呤组血浆中MDA和脊髓组织中HNE含量均显著低于模型组(P<0.05);在伤后12 h,血浆中8-iso-PGF2α含量也显著低于模型组(P<0.05)。结论:合适剂量的甲氨蝶呤防止脊髓继发性损伤可能与其抑制或减轻脂质过氧化有关。