过氧化物酶体增殖物激活受体γ激动剂罗格列酮对减少脊髓损伤后继发损害的作用

Peroxisome proliferator activated receptorγagonist rosiglitazone reduces secondary damage in spinal cord injury

为研究在大鼠创伤性脊髓损伤模型中研究罗格列酮的神经保护作用,成年SD大鼠(n=12/组)分为椎板切开术组(假手术组)、单纯脊髓损伤组、脊髓损伤+罗格列酮治疗组(2mg/kg BID,7d)、脊髓损伤+生理盐水组(溶剂对照组)。脊髓损伤通过硬膜外施加动脉夹实现。脊髓损伤后24h,对脊髓细胞凋亡和肿瘤坏死因子α(TNFα)表达水平、白介素1β(IL-1β)、髓过氧化物酶(MPO)、凋亡相关蛋白B细胞淋巴瘤2(Bcl-2)和B细胞淋巴瘤2相关X蛋白(Bax)进行检测。在脊髓损伤后3、7、10、14、21d进行运动功能测试。结果表明:脊髓损伤后24h,罗格列酮组的TNFα、IL-1β和MPO水平与细胞凋亡显著低于单纯脊髓损伤组和溶剂对照组(P<0.05)。罗格列酮可以逆转脊髓损伤引起的Bax升高和Bcl-2下降。罗格列酮组大鼠比单纯脊髓损伤组和溶剂对照组明显具有更好的恢复功能。罗格列酮显著提高大鼠脊髓损伤后的功能恢复。这一作用可能是通过减少局部炎症因子的浓度和细胞凋亡的表达实现。

To investigate the neuroprotective effects of rosiglitazone in a rat traumatic spinal cord injury（SCI）model,adult Sprague-Dawley rats（n = 12/group）were divided into laminectomy（sham）,SCI,SCI and rosiglitazone treatment（2mg/kg twice daily for 7days）,or SCI and saline injection（vehicle）.SCI was induced via dural application of an aneurysm clip.Spinal cord apoptosis and levels of tumour necrosis factor-α（TNFα）,interleukin（IL）-1b,myeloperoxidase（MPO）and the apoptosisassociated proteins B-cell leukaemia/lymphoma 2（Bcl-2）and Bcl-2associated X protein（Bax）were examined 24 hafter SCI.Locomotor function was evaluated 3,7,10,14,21 days after SCI.The results show that at 24 hafter SCI,apoptosis and TNFα,IL-1band MPO concentrations are significantly lower in the rosiglitazone group than in the vehicle and SCI groups.SCI results in an increase in Bax and a decrease in Bcl-2,which is reversed by rosiglitazone treatment.Rats in the rosiglitazone group have significantly better functional recovery than those in the vehicle and SCI groups.Rosiglitazone significantly improves functional recovery,probably via attenuation of the local inflammatory reaction and reduced apoptosis.