依达拉奉抗大鼠脊髓损伤后脊髓细胞凋亡的机制初探

摘要： 目的 探讨依达拉奉 （EDA） 对大鼠脊髓损伤 （SCI） 后内质网应激 （ERS） 介导的细胞凋亡的影响。方法 36 只 SD 大鼠随机分为假手术(sham)组、 SCI 组、 EDA 组, 每组 12 只。采用 Allen’ s 法建立 SCI 模型, sham 组仅行椎板切除术。术后 Sham 组和 SCI 组给予与 EDA 组等体积等频次生理盐水处理; EDA 组在 SCI 模型建成以后予以 EDA(10 mg/kg), 每 12 h 腹腔注射给药 1 次。于术后 3 d 取脊髓, 应用 Western blot 检测 C/EBP 同源蛋白 （CHOP）、 Cleaved caspase-12 和 Cleaved caspase-3 的表达水平, 免疫荧光技术检测脊髓组织中 caspase-12、 CHOP 阳性细胞的比率, TUNEL 法检测脊髓细胞凋亡水平。结果 SCI 组较 sham 组 CHOP、 Cleaved caspase-12、 Cleaved caspase-3 的表达升高, Cleaved caspase-12、 CHOP 阳性细胞比率增加, 脊髓组织细胞凋亡比率增加 （均 P < 0.01）。EDA 组较 SCI 组 CHOP、 Cleaved caspase-12 和 Cleaved caspase-3 的表达降低, Cleaved caspase-12、 CHOP 阳性细胞比率减少, 脊髓组织细胞凋亡比率减少 （均 P < 0.01）。结论 EDA 对脊髓损伤有保护作用, 机制可能与其抑制 SCI 后脊髓细胞的 ERS 和脊髓细胞的凋亡有关。     

Pro-inflammatory cytokines involvement in the hesperidin antihyperalgesic effects at peripheral and central levels in a neuropathic pain model

Emerging evidence proposes a link between immune changes and pain, which is consistent with the inflammation theory and the increased incidence of neurodegenerative diseases. Flavonoids have long been used because of their anti-inflammatory potential activity and they are considered a promising alternative to alleviate neuropathic pain. The aim of this study was to investigate the antihyperalgesic effect of hesperidin and the presence of pro-inflammatory cytokines evaluated at peripheral and central levels in the chronic constriction injury as model of neuropathic pain in rats. Mechanical and thermal hyperalgesia were assessed in the aesthesiometer and plantar tests, respectively, as related to the presence of cytokines concentrations (TNF-α, IL-1β and IL-6) in sciatic nerve and segments of the spinal cord after 15 days chronic constriction injury model in rats receiving vehicle or hesperidin. Antihyperalgesic response of hesperidin (100 mg/kg) was associated to the presence of cytokines mainly at several sections of the spinal cord suggesting not only peripheral but also its involvement in central sensitization in the experimental neuropathic pain.     

硫化氢对大鼠急性脊髓损伤的保护作用

目的 探讨硫化氢 （H2S） 对大鼠急性脊髓损伤后自噬及细胞凋亡的影响。方法 36 只健康雄性 SD 大鼠随机分为假手术组 （Sham 组）、 单纯脊髓损伤组 （模型组）、 H2S 处理组(H2S 组), 每组 12 只。采用 Allen’ s 法构建大鼠脊髓损伤模型, Sham 组只行椎板切除术, 暴露脊髓不打击; H2S 组在脊髓损伤后 1 h 腹腔注射 50 μmol/kg 硫氢化钠;模型组给予等体积生理盐水。各组脊髓损伤 24 h 后取出脊髓组织, Western blot 检测 LC3、 p70S6K 和 Cleaved caspase-3 表达; 免疫荧光法检测 LC3 表达; TUNEL 染色法检测各组细胞凋亡率。结果 与 Sham 组相比, 模型组 LC3Ⅱ/LC3Ⅰ, Cleaved caspase-3 表达升高,p70S6K 表达降低、 细胞凋亡率升高 （P < 0.01）; 与模型组相比, H2S 组 LC3Ⅱ/LC3Ⅰ、 Cleaved caspase-3 表达降低, p70S6K 表达升高, 细胞凋亡率下降（P < 0.01）。结论 H2S 可抑制大鼠急性脊髓损伤后自噬并减少细胞凋亡。     

选择性线粒体分裂抑制剂对大鼠急性脊髓损伤后神经细胞的保护作用及其机制

【摘要】目的 检测选择性线粒体分裂抑制剂-1（Mdivi-1）对大鼠急性脊髓损伤（ASCI）后神经细胞线粒体中丙二醛（MDA）、谷胱甘肽（GSH）、细胞色素C（Cyt-C）及神经细胞凋亡的影响。方法成年雌性SD大鼠36只,体质量 250~300g,随机分为假手术组（Sham组）、单纯脊髓损伤组（SCI组）、Mdivi-1预处理组（1.20mg/kg,Mdivi-1组）,各12 只。Sham组只暴露脊髓,不打击。SCI组和Mdivi-1组采用Allen’s方法制备脊髓损伤模型。Mdivi-1组在脊髓打击之前15min尾静脉给予Mdivi-1,而SCI组给予等量二甲基亚砜（DMSO）。Sham组在暴露脊髓8h后立即处死,SCI组和Mdivi-1组均于脊髓损伤后8h处死;然后取出脊髓节段T9~T11,用分光光度计检测各组脊髓组织线粒体中MDA 和GSH的含量,Western Blot法检测线粒体及胞浆内Cyt-C表达情况,荧光TUNEL法观察神经细胞凋亡情况。结果与Sham组相比,SCI组线粒体中Cyt-C和GSH明显减少,但线粒体中的MDA,胞浆中Cyt-C及神经细胞凋亡数目明显增多（P<0.01）;与SCI组相比,Mdivi-1组线粒体中Cyt-C和GSH明显增多,但线粒体中MDA,胞浆中Cyt-C以及神经细胞凋亡数目明显减少（P<0.01）。结论Mdivi-1具有减轻ASCI后神经细胞线粒体氧化损伤,抑制线粒体中Cyt-C 的释放及神经细胞凋亡的作用,促进了脊髓功能恢复。     

Neuroprotective Effect of Ginsenoside Rd in Spinal Cord Injury Rats

In this study, the neuroprotective effects of ginsenoside Rd (GS Rd) were evaluated in a rat model of spinal cord injury (SCI). Rats in SCI groups received a T8 laminectomy and a spinal contusion injury. GS Rd 12.5, 25 and 50 mg/kg were administered intraperitoneally 1 hr before the surgery and once daily for 14 days. Dexamethasone 1 mg/kg was administered as a positive control. Locomotor function was evaluated using the BBB score system. H&E staining and Nissl staining were performed to observe the histological changes in the spinal cord. The levels of MDA and GSH and the activity of SOD were assessed to reflect the oxidative stress state. The production of TNF‐α, IL‐1β and IL‐1 was assessed using ELISA kits to examine the inflammatory responses in the spinal cord. TUNEL staining was used to detect the cell apoptosis in the spinal cord. Western blot analysis was used to examine the expression of apoptosis‐associated proteins and MAPK proteins. The results demonstrated that GS Rd 25 and 50 mg/kg significantly improved the locomotor function of rats after SCI, reduced tissue injury and increased neuron survival in the spinal cord. Mechanically, GS Rd decreased MDA level, increased GSH level and SOD activity, reduced the production of pro‐inflammatory cytokines and prevented cell apoptosis. The effects were equivalent to those of dexamethasone. In addition, GS Rd effectively inhibited the activation of MAPK signalling pathway induced by SCI, which might be involved in the protective effects of GS Rd against SCI. In conclusion, GS Rd attenuates SCI‐induced secondary injury through reversing the redox‐state imbalance, inhibiting the inflammatory response and apoptosis in the spinal cord tissue.     

基于7T动物磁共振成像研究改良Allen’s法制作脊髓外伤动物模型之细胞过度凋亡机制

目的本研究拟采用改良Allen’s法制作SCI动物模型,通过检测致伤脊髓组织mi R-16的表达探究SCI后细胞过度凋亡的可能机制。方法36只成年SD大鼠随机分为正常组(12只)、假手术组(12只)、模型组(12只),通过改良Allen’s制作SCI模型,观察各组行为学评分(BBB评分)、病理表现及PCR法检测mi R-16的表达。结果模型组在术后3 d及7 d的BBB评分与正常组和假手术组对比差异有统计学意义(P <0.01)。模型组中的mi R-16表达较正常组和假手术组显著升高(P <0.01)。结论研究认为mi R-16参与改良Allen’s法制作大鼠SCI模型后引发神经细胞过度凋亡机制。     

簇集蛋白在大鼠急性脊髓损伤组织中的表达及其意义

目的　探讨簇集蛋白 (clusterin)在急性脊髓损伤组织中的表达及其在继发性脊髓损伤中可能发挥的重要作用。方法　采用改良Allen重物打击法制成SD大鼠脊髓急性损伤模型 ,通过苏木素 伊红 (HE)染色及免疫组织化学染色观察损伤组和假手术组伤后 0. 5、1、3、7、14、2 1d脊髓损伤组织变性坏死及簇集蛋白的表达情况。结果　损伤组在伤后 1d簇集蛋白阳性表达开始增加 ,约在伤后 7d达到高峰 ,之后表达逐渐减少 ,伤后2 1d趋于稳定 ,随时间延长存在动态变化过程 ,并与脊髓损伤程度相一致。损伤组在伤后 1、3、7、14、2 1d簇集蛋白表达与假手术组及正常对照组差异有统计学意义 (P <0 . 0 1) ;假手术组及正常对照组伤后各时间点均有簇集蛋白阳性表达 ,但表达随时间延长无动态变化过程。结论　簇集蛋白在急性脊髓损伤组织中表达明显增加 ,并可能通过补体调节、抗凋亡及热休克蛋白活性等机制减轻继发性脊髓损伤。     

外伤性背侧脊髓损伤对膀胱排尿神经通路的影响

目的采用伪狂犬病毒(PRV)示踪技术观察大鼠背侧胸腰脊髓损伤(SCI)所致的膀胱排尿神经通路改变。方法清洁级雌性SD大鼠24只,采用随机数字表法分为2组:假手术组12只和背侧SCI损伤组12只。使用标准化SCI动物模型实验装置来制备动物模型,损伤部位定于T12～L1水平,假手术组大鼠仅咬除棘突及椎板,不损伤脊髓。SCI由背侧损伤脊髓,模型制备后,即刻对无SCI、SCI大鼠膀胱壁注射PRV,注射后96h直接取材,免疫组织化学方法显示大鼠脊髓切片中PRV阳性神经元。结果 PRV阳性神经元经免疫组织化学显色后呈棕黄色,观察切片SCI平面以上及以下均出现阳性神经元。SCI节段平面以上切片与对照组比较,阳性神经元显著减少;节段平面以下切片与对照组比较,阳性神经元增加。结论 SCI后,损伤导致受伤脊髓节段以上排尿反射通路受阻,进而SCI平面以下膀胱排尿反射通路发生代偿。     

骨髓间充质干细胞移植对大鼠脊髓半切损伤的修复作用

目的：观察骨髓间充质千细胞（MSC）移植对脊髓半切损伤大鼠运动功能的修复作用。方法：20只成年D大鼠随机分为移植组（n=10）和对照组（n=10），均进行脊髓半切损伤。伤后1周，移植组于伤处移植大鼠MSC，而对照组仅注射等量PBS。分别于移植后1天、1周、2周、3周、4周用BBB评分观测大鼠的运动功能，并于移植后4周进行损伤脊髓的大体观察和组织学检测。结果：移植后1周两组动物运动功能恢复无明显差异。移植后2周、3周、4周，与对照组比较，移植组显著提高运动功能。移植后4周，移植组损伤脊髓的结构修复明显优于对照组。结论：脊髓半切损伤大鼠经MSC移植后能明显改善其运动功能和神经形态，MSC移植对脊髓半切损伤大鼠有治疗作用。     

辛伐他汀对脓毒症小鼠肺损伤的保护作用

目的观察辛伐他丁对脓毒症小鼠急性肺损伤的保护作用,并探讨其可能机制。方法采用盲肠结扎穿孔术制备脓毒症小鼠模型,将72只雄性C57BL/6小鼠随机分成3组:假手术组、脓毒症急性肺损伤组(脓毒症组)、脓毒症+辛伐他汀治疗组(治疗组)。治疗组给予辛伐他汀0.2μg/g,q12h腹腔注射1周;假手术组、脓毒症组给予等量安慰剂腹腔注射1周。分别于造模后6、12、24 h留取肺脏标本。HE染色观察肺组织病理学变化,免疫组化检测肺组织toll样受体4(Toll-like receptor 4,TLR4)蛋白的表达,ELISA测定肺组织匀浆中IL-1β及TNF-α的表达水平。结果与假手术组比较,造模后6、12、24 h,脓毒症组肺组织病理学评分、肺组织TLR4蛋白的表达,以及TNF-α、IL-1β水平明显升高(P<0.05);与脓毒症组相比,治疗组上述指标明显降低(P<0.05)。结论辛伐他汀通过抑制TLR4信号转导通路,减少其下游炎症介质TNF-α、IL-1β的释放,对脓毒症导致的急性肺损伤具有一定保护作用。     

依达拉奉对急性脊髓损伤后的大鼠神经组织氧化损害保护作

目的 探讨依达拉奉对急性脊髓损伤后的大鼠神经组织保护机制.方法 90只SD大鼠随机分为假手术组(n=30),ASCI对照组(n=30)和依达拉奉干预组(n=30),采用改良的Allen法,制成中度脊髓损伤大鼠模型;每组分别于6h、12h、24h、48h、72h5个时点,每个时点6只大鼠,检测各组各时点血清及脊髓中的NO、SOD、MDA的含量及脊髓组织含水量变化;TUNEL法检测72h后各组脊髓中的神经细胞凋亡及Caspase-3mRNA阳性细胞.结果 对照组各时点SOD活性明显低于假手术组,而NO、MDA含量明显高于假手术组,对照组各时点含水量与SOD活性呈明显负相关,与MDA含量呈明显正相关,依达拉奉干预组各时点SOD活性明显高于对照组,而NO、MDA含量明显低于对照组,依达拉奉干预组各时点含水量与SOD活性呈明显负相关,与MDA含量呈明显正相关,假手术组脊髓中无或偶见凋亡细胞及阳性染色细胞,对照组可见大量凋亡细胞及阳性染色细胞,依达拉奉干预组凋亡细胞及阳性染色细胞数量较对照组明显减少.结论 依达拉奉通过有效地清除氧自由基,可明显抑制急性脊髓损伤后的脂质过氧化反应及降低神经细胞的凋亡,从而达到保护其神经组织的作用.     

低温预处理对脊髓损伤早期保护作用的实验性研究

目的 观察低温预处理对大鼠脊髓损伤早期病理形态学及运动功能的影响.方法 应用改良Tarlov评分对大鼠脊髓损伤模型进行神经运动功能评价.结果 低温预处理损伤组（B组）脊髓损伤早期病理形态学改变较损伤对照组（C组）轻,损伤中心区残留白质面积大于C组[（1.17±0.15）mm2与（0.94±0.11）mm2],而微囊计数明显低于C组（7.43±1.40与13.46±1.77）,差异均有统计学意义（均P＜0.01）;B组神经运动功能评分（改良Tarvo评分）明显高于C组[（4.1±0.7）分与（2.4±1.0）分],差异有统计学意义（P＜0.01）.结论 低温预处理对大鼠正常脊髓形态结构及神经运动功能无明显影响,但可明显减轻大鼠脊髓损伤早期病理形态学损害,减少损伤中心区白质面积的丢失,改善脊髓损伤早期神经运动功能状况.     

Dose-related neuropathic and anti-neuropathic effects of simvastatin in vincristine-induced neuropathic pain in rats

The present study explores the role of simvastatin in vincristine-induced neuropathic pain, which was induced by administering vincristine (100 µg/kg i.p.) for 10 days (two 5 day cycles with 2 days pause). Pain was assessed by determining mechanical hyperalgesia, mechanical dynamic allodynia, heat hyperalgesia and cold allodynia. Biochemically, myeloperoxidase (MPO) activity was measured along with serum cholesterol levels. Simvastatin (7.5, 15 and 30 mg/kg) was administered for 14 days after administration of vincristine. Simvastatin (7.5 and 15 mg/kg) reversed vincristine-induced neuropathic pain and attenuated vincristine-induced increase in MPO, without altering cholesterol levels. Simvastatin at higher dose (30 mg/kg) did not alter neuropathic pain despite decreasing MPO levels. Furthermore, administration of simvastatin (30 mg/kg i.p.) in vincristine treated rats as well as it's per se administration in normal rats reduced cholesterol levels. Per se administration of simvastatin in normal rats produced neuropathic pain. It is concluded that simvastatin attenuates neuropathic pain only at lower doses with no reduction in cholesterol levels and anti-inflammatory effects may possibly reverse neuropathic pain. However, despite reducing inflammation, simvastatin did not confer beneficial effects at higher doses at which there is reduction in cholesterol levels, suggesting the critical role of cholesterol in neuropathic pain induction.     

缺血后处理增加脊髓miR-125b表达减轻大鼠脊髓缺血-再灌注损伤后神经元凋亡

目的观察缺血后处理(Ischemic postconditioning,IPC)对大鼠脊髓缺血再灌注损伤(Spinal cord ischemia reperfusion injury,SCIRI)后microRNA(miRNA,miR)-125b表达及下肢运动功能的影响。方法 45只SD大鼠平均随机分为3组:假手术组(Sham组)、缺血-再灌注组(IR组)和缺血后处理组(IPC组)。Sham组仅暴露主动脉弓而不夹闭,其他各组夹闭主动脉弓14 min后再开放建立SCIRI模型。IPC组于再灌注5 min后给予5循环缺血后适应。再灌注后24 h,处死大鼠,提取脊髓组织,分别检测脊髓组织湿/干重比(Wet-dry ratio,W/D)和总含水量(Total water content,TWC),HE染色观察脊髓组织病理学变化,qRT-PCR测定脊髓组织中miR-125b表达,TUNEL法检测神经元凋亡数量(Apoptotic quantitiy,AQ)。结果术后24 h,与Sham组比较,IR组大鼠脊髓W/D、TWC、AQ升高,脊髓组织中miR-125b表达下调(P<0.05);与IR组比较,IPC组脊髓W/D、TWC、AQ降低,脊髓组织中miR-125b表达上调(P<0.05)。HE染色显示,Sham组脊髓前角结构完好,可见大量胞核完整的运动神经元,IR组脊髓前角内大量空泡形成,神经元结构缺失,胞质呈嗜酸性,而IPC组脊髓前角存在部分结构正常的神经元。结论缺血后处理可能通过上调脊髓组织中miR-125b的表达,减少脊髓组织前角运动神经元凋亡,从而改善大鼠SCIRI损伤。     

银杏叶提取物EGb761对大鼠脊髓损伤后的神经保护作用

目的探讨银杏叶提取物EGb761对实验性大鼠脊髓损伤后神经保护的作用及其机制。方法成年雄性SD大鼠132只,体重200～250 g,随机分为正常对照组（N组）、损伤组（T组）、甲基强的松龙治疗组（MP组）和EGb761治疗组（EGb761组）,每组33只。T组、MP组、EGb761组用改良Allen法以25GCF损伤力度致伤大鼠,建立T9脊髓中度损伤模型。术后4、8、24 h每组随机取3只动物切取损伤区1 cm脊髓节段,分别用黄嘌呤氧化酶法和硫代巴比妥酸（TBA）法测定脊髓组织中超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量。分别于术后24 h、3、5、7、14 d处死动物（n=6）,快速取T9节段脊髓,TUNEL法标记细胞凋亡,免疫组化方法检测诱生型一氧化氮合酶（iNOS）的表达。结果术后4、8、24 h EGb761治疗组SOD活性及MDA含量与损伤对照组比较均差异有显著性（P〈0.01）。术后各时相点EGb761治疗组神经细胞凋亡指数和iNOS表达阳性细胞率均低于损伤对照组（P〈0.01或P〈0.05）。结论 EGb761能抑制脊髓损伤后的脂质过氧化反应,减轻神经细胞的凋亡,其机制可能与抑制iNOS表达有关。     

Blockade of 5-HT7 receptors reduces tactile allodynia in the rat

This study assessed the role of systemic and spinal 5-HT₇ receptors on rats submitted to spinal nerve injury. In addition, the 5-HT₇ receptors level in dorsal root ganglion and spinal cord was also determined. Tactile allodynia was induced by L5/L6 spinal nerve ligation. Systemic (0.01-10 mg/kg) or spinal (0.3-30 μg) administration of the selective 5-HT₇ receptor antagonist SB-269970 but not vehicle reduced in a dose-dependent manner established tactile allodynia. This effect was maintained for about 6 h. SB-269970 was more potent and effective by the spinal administration route than through systemic injection. Spinal nerve ligation reduced expression of 5-HT₇ receptors in the ipsilateral but not contralateral dorsal root ganglia. Moreover, 5-HT₇ receptor levels were lower in the ipsilateral dorsal spinal cord of neuropathic rats compared to naïve and sham rats. No changes in the receptor levels were observed in the contralateral dorsal spinal cord and in both regions of the ventral spinal cord. Data suggest that spinal 5-HT₇ receptors play a pronociceptive role in neuropathic rats. Results also indicate that spinal nerve injury leads to a reduced 5-HT₇ receptors level in pain processing-related areas which may result from its nociceptive role in this model. Data suggest that selective 5-HT₇ receptor antagonists may function as analgesics in nerve injury pain states.     

细胞凋亡在脊髓损伤中的表达及意义

目的：探讨细胞凋亡在脊髓损伤发病机理中的作用。方法：采用Allen氏方法制作大鼠脊髓损伤模型，用HE染色及原位末端标记法，对大鼠脊髓损伤后不同时间脊髓组织中凋亡细胞的数目进行观察和分析，并作正常对照。结果：损伤后灰质和白质均检测到凋亡细胞，细胞凋亡发生在损伤后2h-4周，以3d时达到高峰，至4周时渐趋于正常。结论：大鼠脊髓损伤后神经细胞存在死亡和凋亡两种方式，对研究脊髓损伤的病理生理过程有重要意义。     

运动训练对脊髓损伤大鼠脊髓内BDNF及其受体TrkB表达的影响

目的 研究运动训练对脊髓损伤（SCI）大鼠脊髓内脑源性神经营养因子（BDNF）及其酪氨酸激酶受体B（TrkB）表达的影响,探讨运动训练促进脊髓损伤功能恢复的可能机制。方法 24只成年雌性SD大鼠随机分为假手术组、损伤对照组和运动训练组。采用通用型脊髓打击器建立大鼠T10脊髓损伤模型。损伤后7天起,对SCI大鼠进行4周运动训练,假手术组和损伤对照组不进行运动训练。损伤前及损伤后第1、2、3、4、5周采用BBB评分评定运动功能。运动训练结束后(即损伤后5周)取大鼠T12～L1节段脊髓,免疫组织化学检测脊髓内BDNF和TrkB表达及分布,Western blot检测脊髓内BDNF和TrkB蛋白含量。结果 运动训练组和损伤对照组BBB评分均较损伤后第1、2周明显提高,运动训练组较损伤对照组增加更为显著（P<0.05）。BDNF免疫反应阳性产物多分布于脊髓前角,脊髓后角及中央管周围也有出现;运动训练组BDNF阳性染色颗粒增多,平均光密度值较假手术组及损伤对照组均显著增加（P<0.05）。TrkB免疫反应阳性产物于脊髓前角、后角、中央管周围等处均出现较多分布;运动训练组TrkB阳性染色颗粒增多,平均光密度值较假手术组及损伤对照组均显著增加（P<0.05）。Western blot结果显示运动训练组大鼠脊髓内BDNF及TrkB的表达较假手术组、损伤对照组均明显增加(P＜0.05)。结论 运动训练能诱导脊髓损伤大鼠脊髓内BDNF及其受体TrkB表达,促进SCI大鼠运动功能恢复。     

β-干扰素对大鼠急性脊髓损伤后神经功能恢复的影响

目的 初步探讨β-干扰素对大鼠急性脊髓损伤后神经功能恢复的影响.方法 SD成年大鼠40只随机分成A组(脊髓损伤组)、B组(甲基强的松龙干预组)、C组(β-干扰素干预组)、D组(假手术组)各10只,用改良的Allen装置撞击大鼠脊髓胸9~10节段建立脊髓损伤模型,术后各组予相应干预处理.采用BBB评分、改良Tarlov评分和斜板实验方法观察大鼠行为学改变情况,于术后第1、3、7、14和21天对大鼠急性脊髓损伤后不同时段的脊髓神经功能进行评分.结果 大鼠急性脊髓损伤后BBB评分、改良Tarlov评分和斜板实验分值均近0,随着时间进展评分逐渐升高,B、C组升高明显,干预治疗的B、C组与A组相比7 d内无显著变化(P>0.05),14 d时有显著变化(P<0.05);但B组与C组比较无显著变化(P>0.05).结论 β-干扰素应用有利于大鼠急性脊髓损伤后神经功能恢复,其作用机制需要进一步研究.     

Celastrol inhibits microglial pyroptosis and attenuates inflammatory reaction in acute spinal cord injury rats

Pyroptosis pathway is closely related to inflammation. However, Celastrol effect on pyroptosis pathway after spinal cord injury (SCI) are poorly understood. We studied the anti-inflammatory and neuroprotective effects of Celastrol on acute spinal cord injury in rats, and its anti-inflammatory effects on lipopolysaccharide (LPS)/ATP-induced microgliosis. Our results show that Celastrol can improve the recovery of hindlimb motor function after SCI in Sprague-Dawley (SD) rats, and reduce the cavity area of spinal cord injury along with the neuronal loss. Celastrol simultaneously reduced the activation of microglia (especially M1 microglia) in the spinal cord, inhibited the pyroptosis-related proteins (NLRP3 ASC Caspase-1 GSDMD), reduced the release of TNF-α IL-1β and IL-18 inflammatory factors, and increased the release of IL10 cytokines. In vitro studies showed that Celastrol reduced the toxicity resulting from the administration of LPS with ATP to BV-2 cells, inhibited the pyroptosis-related proteins (NLRP3 Caspase-1 GSDMD), and inhibited the release of corresponding inflammatory factors. Finally, Celastrol can inhibit the expression of NFκB/p-p65 in vitro and in vivo. Our results show that Celastrol can attenuate the inflammatory response of the spinal cord after SCI, which is associated with inhibition of microglial activation and pyroptosis pathway. Further study to explore the use of Celastrol to treat SCI is warranted.