阿托伐他汀治疗实验性自身免疫性脑脊髓炎

The Treatment of Experimental Autoimmune Encephalomyelitis in Wistar Rats by Atorvastatin

目的探讨阿托伐他汀对Wistar大鼠实验性自身免疫性脑脊髓炎(EAE)的治疗作用。方法建立Wistar大鼠EAE模型,给予不同剂量阿托伐他汀处理,观察大鼠发病程度、病理改变及血清白细胞介素4(IL-4)、干扰素-γ(IFN-γ)水平的变化。结果阿托伐他汀可减轻大鼠发病程度,减少炎性病灶数,降低血清IFN-γ水平升高幅度,使血清IL-4水平在发病初期即升高,高剂量阿托伐他汀作用更显著。结论阿托伐他汀在一定程度上可有效干预大鼠EAE发病,并呈剂量相关性,其机制可能与改变Th1/Th2类细胞因子比值有关。

Objective This study was designed to explore the effects of atorvastatin, an inhibitor of HMG-GoA reduetase on the experimental autoimmune eneephalomyelitis（EAE） in Wistar rats. Methods Atorvastatin was administered at two different doses to Wistar rats EAE model. A scale of 0--5 according to the symptoms scored the severity of EAE. The numbers of inflammation lesion in the brain and spinal cord were counted by optical microscopy. The serum levels of interferon-γ and interleukin-4 were determined by enzyme-linked immunosorbent assay. Results Compared to the untreated group, the atorvastatin groups only partially developed EAE with a lighter degree of malfunction. The numbers of inflammation lesion redueed signifieantly in atorvastatin treated groups. The serum level of interferon-γ increased in atovarstatin treated groups with the development of EAE, but was lower than that in the untreated group. The serum levels of interleukin-4 in atorvastatin groups were higher at the onset. Higher dose atorvastatin showed better protection against ERE development. Conclusion To a certain extent atorvastatin could effectively ameliorate EAE in rats. The effects were in a dose-dependent fashion, which might be mechanistically related to the balance between Th1/Th2 eytokines.