α-硫辛酸对EAE大鼠的保护作用和机制探讨

摘要

目的研究α⁃硫辛酸（ alpha⁃lipoic acid， ALA ）在实验性变态反应性脑脊髓炎（ experimental autoimmune encephalomyelitis， EAE）大鼠模型中对脊髓组织的保护作用并探讨其机制。方法 Wistar大鼠随机分为对照组（ NC组）、EAE组（ EAE组）和α⁃硫辛酸组（ ALA组）。对照组不接受任何处理，EAE组接受免疫注射， ALA组在EAE组基础上加用ALA治疗。采用Kono评分法进行大鼠神经功能评估，在实验60 d时取材，观察脊髓腰膨大段组织的病理学改变，以免疫组化方法标记白介素⁃17（ IL⁃17），观察其表达变化，分光光度计检测脑组织中还原型谷胱甘肽（ glutathione， GSH）、丙二醛（ malondialdehyde， MDA）的含量。结果 EAE组出现明显的神经功能障碍，ALA组大鼠神经功能明显改善（ P＜0�05）；免疫细胞化学染色结果显示，EAE组大鼠脊髓腰膨大炎症标记物IL⁃17蛋白的表达比NC组明显增加（ P＜0�05）；ALA治疗后IL⁃17蛋白的表达显著降低（ P＜0�05）；与 NC组相比，EAE组大鼠脑组织中GSH含量明显下降（P＜0�05），MDA含量明显增加（P＜0�05），ALA治疗后显著增加了GSH含量（ P＜0�05），降低了MDA含量（ P＜0�05）。结论 ALA可能是通过抑制炎症反应和减轻氧化应激发挥了在EAE大鼠模型中的保护作用。%Objective To explore the effects of alpha⁃lipoic acid ( ALA) on experimental allergic encephalomy⁃elitis ( EAE) and the possible mechanisms. Methods Female Wistar rats were randomly divided into three groups:normal control group( NC group) , EAE model group ( EAE group) , and the ALA administrated EAE model group ( ALA group) . Kono scale was used to evaluate neurofunction deficiency. Immunohistochemistry was used to detect the expression of IL⁃17 in the spinal cord on the 60th day of the disease course. Spectrophotometry was used to detect the levels of malondialdehyde( MDA) and glutathione( GSH) in the brain. Results In EAE group, the score of Kono scale was significantly higher( P<0�05) , the expression of IL⁃17 significantly increased, MDA significantly increased ( P<0�05) , and GSH significantly decreased( P<0�05) . However, ALA could effectively improve neurofunction( P<0�05) , decrease the expression of IL⁃17 ( P<0�05) , decrease the level of MDA( P<0�05) , and increase the level of GSH( P<0�05) . Conclusions ALA may exert its neuroprotective effect through ameliorating inflammative reacts and oxidative stress.