阿托伐他汀治疗实验性自身免疫性脑脊髓炎.docVIP

阿托伐他汀治疗实验性自身免疫性脑脊髓炎 目录 TOC \o 1-9 \h \z \u 目录 1 正文 1 文1：阿托伐他汀治疗实验性自身免疫性脑脊髓炎 1 1 材料和方法 3 2 结果 4 文2：阿托伐他汀治疗实验性自身免疫性脑脊髓炎 5 1 材料和方法 7 2 结果 8 3 讨论 10 参考文摘引言： 12 原创性声明（模板） 13 文章致谢（模板） 14 正文 阿托伐他汀治疗实验性自身免疫性脑脊髓炎 文1：阿托伐他汀治疗实验性自身免疫性脑脊髓炎 ABSTRACT: Objective This study was designed to explore the effects of atorvastatin, an inhibitor of HMGCoA reductase on the experimental autoimmune encephalomyelitis(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 numbe 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 numbe of inflammation lesion reduced significantly in atorvastatin treated groups. The serum level of interferonγ increased in atovatatin 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 oet. Higher dose atorvastatin showed better protection agait EAE 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 cytokines. KEY WORDS: experimental autoimmune encephalomyelitis; atorvastatin; IL4; IFNγ 多发性硬化(multiple sclerosis,MS)是一种由免疫细胞介导攻击中枢神经系统髓鞘为特征的自身免疫性疾病,好发于青壮年,是青壮年人群致残的常见疾病之一。目前临床上经美国FDA批准用于治疗MS的药物有:β干扰素(IFNβ)、格拉默(Glatiramer acetate)和米托蒽醌(Mitoxantrone)等。这些药物作用有限,且有非肠道给药、价格昂贵、不良反应发生率高等缺点,故有必要寻找新的更安全有效的治疗药物。他汀类药物主要用于降脂治疗,近年来发现其具有独立于降脂作用的免疫调节作用的多效性[1]。笔者研究阿托伐他汀对人MS的经典动物模型——实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)模型的影响,探讨其在EAE中的可能作用机制。 1 材料和方法 1.