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目的:研究α-硫辛酸(ALA)对实验大鼠变态反应性脑脊髓炎(EAE)的作用。方法:用豚鼠6只制备实验用免疫抗原。选择Wistar大鼠30只,随机分为5组(n=6):(1)正常对照组(NC组);(2)EAE-7 d和(3)EAE-14 d组,于皮下注射抗原匀浆观察7 d和14 d;(4)ALA-7 d和(5)ALA-14 d组,于第1次发病时给予ALA腹腔注射,连续用7 d和14 d。在研究时间点处死大鼠,HE染色观察病理学改变,免疫细胞化学染色观察白介素-17(IL-17)的表达,同时测定大鼠脑组织丙二醛(MDA)和还原型谷胱甘肽(GSH)。结果:HE染色显示,在α-硫辛酸治疗的ALA-7 d和14 d组,均能减轻脊髓组织的炎性反应和髓鞘损伤。免疫细胞化学染色表明,EAE大鼠IL-17蛋白表达明显增加(P<0.05~0.01),经α-硫辛酸处理后IL-17蛋白表达降低并于14 d接近对照水平。与NC组比较,EAE组大鼠MDA含量明显升高,GSH则明显降低;经ALA处理后,MDA显著降低,而GSH则明显增加(P<0.05~0.01)。相关性分析表明,IL-17表达与MDA含量呈正相关(r=0.466,P<0.05),而与GSH含量则呈负相关(r=-0.478,P<0.05)。结论:在EAE大鼠模型中ALA可以改善和缓解炎症反应,其保护作用可能通过调节IL-17表达实现,并表现为MDA和GSH含量的变化。
Objective: To investigate the effect of α-lipoic acid (ALA) on experimental rat allergic encephalomyelitis (EAE). Methods: 6 guinea pigs were used to prepare experimental immunogens. Thirty Wistar rats were randomly divided into 5 groups (n = 6): (1) normal control group (NC group); (2) EAE-7 d and (4) ALA-7 d and (5) ALA-14 d groups were given intraperitoneal injection of ALA at the first incidence for 7 days and 14 days. The rats were sacrificed at the time points of the study, pathological changes were observed by HE staining, the expression of interleukin-17 (IL-17) was observed by immunocytochemistry, and the levels of malondialdehyde (MDA) and reduced glutathione (GSH). Results: The results of HE staining showed that both ALA-7 and 14-day treatment of a-lipoic acid could reduce the inflammatory reaction and myelin damage in spinal cord. Immunocytochemical staining showed that the expression of IL-17 protein in EAE rats increased significantly (P <0.05 ~ 0.01), and the expression of IL-17 protein decreased after treated with α-lipoic acid and approached the control level on the 14th day. Compared with NC group, the content of MDA in EAE group was significantly increased and GSH was significantly decreased. After ALA treatment, MDA decreased significantly, while GSH increased significantly (P <0.05 ~ 0.01). Correlation analysis showed that IL-17 expression was positively correlated with MDA content (r = 0.466, P <0.05), but negatively correlated with GSH content (r = -0.478, P <0.05). CONCLUSION: ALA can ameliorate and relieve the inflammatory reaction in EAE rat model. The protective effect of ALA may be through the regulation of IL-17 expression and the change of MDA and GSH content.