托吡酯对大鼠脊髓损伤后神经的保护机制

关键词：托吡酯  脊髓损伤  氧化应激  细胞凋亡

Keywords:topiramate  spinal cord injury  oxidative stress  apoptosis

摘要：

      摘要 目的：观察托吡酯（TPM）对大鼠脊髓损伤（SCI）后氧化应激及细胞凋亡的影响。 方法：采用改良Allen's法制作大鼠SCI模型，随机分为假手术组、模型组及TPM低、中、高剂量组，采用BBB评分及斜板试验评价各组大鼠后肢运动功能的改变，HE染色观察脊髓形态学变化，紫外分光光度计检测大鼠脊髓组织丙二醛（MDA）和谷胱甘肽（GSH）含量，Western blot法观察脊髓B细胞淋巴瘤基因-2（Bcl-2）及Bcl-2相关X蛋白（Bax）的表达情况。 结果:伤后各组BBB评分及斜板试验结果显著下降，1d、3d各组间差异不显著（P>0.05），伤后5d高剂量组恢复情况显著优于低、中剂量组及模型组（P<0.05）；伤后14d时各组脊髓切片HE染色示高剂量组脊髓病理改变明显轻于低、中剂量组及模型组；与模型组比较，SCI后24h高剂量组MDA含量显著降低（P<0.01），GSH含量显著增加（P<0.01）；高剂量组Bcl-2表达上调（P<0.01），而Bax表达下调（P<0.01）。 结论：TPM可有效降低SCI后的氧化应激水平，抑制细胞凋亡，减轻脊髓继发性损害，促进SCI后神经功能的恢复。

Abstract:

      Abstract Objective:To investigate the effect of topiramate(TPM) on oxidative stress and apoptosis in rats after spinal cord injury（SCI）. Method:The model of SCI in rat was induced by the modified Allen's method. The female Wistar rats were divided randomly into shame group, SCI group,TPM-20，40 and 80 mg/kg groups. Rats' behavioral changes were measured by Basso-Beattie-Bresnaban(BBB) scale and inclined plate test. HE staining was used to observe the morphological changes. The malondialdehyde(MDA) and glutathione(GSH) content and the expressions of B cell lymphoma 2(Bcl-2) and Bcl-2 associated X protein(Bax) were detected at 24h after SCI. Result:The BBB scores and inclined plate test degrees decreased significantly in each group after SCI, the results were not significant different each other at 1 and 3d after SCI(P>0.05),however in high dose TPM group the hindlimb motor function improved markedly compared with other groups at 5d after SCI(P<0.05); pathological changes reduced strikingly in high dose TPM group compared with other groups at 14d after SCI. The MDA contents reduced significantly and the GSH contents increased strikingly(P<0.01) in high dose TPM group compared with model group. Compared with SCI group, in high dose/TPM group the expressions of Bcl-2 were up-regulated and the expression of Bax were down-regulated at 24h after SCI(P<0.01). Conclusion:TPM may play an important role in suppressing the oxidative stress and neuron cells apoptosis after SCI, can reduce the secondary damage of spinal cord and promote the recovery of neuron function.