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过氧化物酶体增殖物激活受体γ激动剂罗格列酮可减轻实验性脊髓损伤中的继发性损伤。

Peroxisome proliferator-activated receptor-γ agonist rosiglitazone reduces secondary damage in experimental spinal cord injury.

作者信息

Li Xigong, Du Junhua, Xu Sanzhong, Lin Xiangjin, Ling Zhiheng

机构信息

Department of Orthopaedic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

出版信息

J Int Med Res. 2013 Feb;41(1):153-61. doi: 10.1177/0300060513476601. Epub 2013 Jan 24.

DOI:10.1177/0300060513476601
PMID:23569141
Abstract

OBJECTIVE

To investigate the neuroprotective effects of rosiglitazone in a rat traumatic spinal cord injury (SCI) model.

METHODS

Adult Sprague-Dawley rats (n = 12/group) underwent laminectomy (sham), SCI, SCI and rosiglitazone treatment (2 mg/kg twice daily for 7 days), 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)-1β, myeloperoxidase (MPO) and the apoptosis-associated proteins B-cell leukaemia/lymphoma 2 (Bcl-2) and Bcl-2 associated X protein (Bax) were examined 24 h after SCI. Locomotor function was evaluated 3, 7, 10, 14 and 21 days after SCI.

RESULTS

At 24 h after SCI, apoptosis and TNFα, IL-1β and MPO concentrations were significantly lower in the rosiglitazone group than in the vehicle and SCI groups. SCI resulted in an increase in Bax and a decrease in Bcl-2, which was reversed by rosiglitazone treatment. Rats in the rosiglitazone group had significantly better functional recovery than those in the vehicle and SCI groups.

CONCLUSION

Rosiglitazone significantly improved functional recovery, probably via attenuation of the local inflammatory reaction and reduced apoptosis.

摘要

目的

研究罗格列酮在大鼠创伤性脊髓损伤(SCI)模型中的神经保护作用。

方法

成年Sprague-Dawley大鼠(每组12只)接受椎板切除术(假手术)、脊髓损伤、脊髓损伤加罗格列酮治疗(2毫克/千克,每日两次,共7天)或脊髓损伤加生理盐水注射(对照)。通过在硬脑膜上应用动脉瘤夹诱导脊髓损伤。在脊髓损伤后24小时检测脊髓细胞凋亡以及肿瘤坏死因子-α(TNFα)、白细胞介素(IL)-1β、髓过氧化物酶(MPO)水平和凋亡相关蛋白B细胞淋巴瘤/白血病-2(Bcl-2)和Bcl-2相关X蛋白(Bax)。在脊髓损伤后3、7、10、14和21天评估运动功能。

结果

脊髓损伤后24小时,罗格列酮组的细胞凋亡以及TNFα、IL-1β和MPO浓度显著低于对照和脊髓损伤组。脊髓损伤导致Bax增加和Bcl-2减少,而罗格列酮治疗可逆转这种变化。罗格列酮组大鼠的功能恢复明显优于对照和脊髓损伤组。

结论

罗格列酮可能通过减轻局部炎症反应和减少细胞凋亡,显著改善功能恢复。

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