阿托伐他汀在实验性变态反应性脑脊髓炎中的作用机制研究  

Study on the mechanism of action of atorvastatin for experimental autoimmune encephalomyelitis

作　　者：高聪[1] 郑建筝[1] 区腾飞[1] 杨洁[1] 

机构地区：[1]广州医学院第二附属医院神经内科,510260

出　　处：《实用医学杂志》2008年第1期20-23,共4页The Journal of Practical Medicine

基　　金：广东省科技计划项目(编号:2006B36004006);广州市科技计划项目(编号:2006J1-C0231);广州市属高校科技项目(编号:61022);番禺区科技计划项目(编号:2006-Z-44-1)

摘　　要：目的:观察阿托伐他汀对SD大鼠实验性变态反应性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)的治疗效果,初步探讨其治疗机制。方法:采用同种脑脊髓匀浆诱导EAE模型,给予阿托伐他汀进行实验性干预治疗,观察和比较动物的神经症状和病理改变。用免疫组化法观察各组动物小胶质细胞反应,用免疫组化法、ELISA法观察脑组织及外周血中TNF-α的表达。结果:阿托伐他汀可以缓解临床症状、缩短病程、降低EAE的缓解率、复发率,减轻炎症反应及脱髓鞘(P<0.05)。治疗组大鼠脑组织中小胶质细胞的阳性细胞数、TNF-α的阳性细胞数及外周血中TNF-α的含量在高峰期与未治疗组相比,差异有统计学意义。结论:阿托伐他汀抑制小胶质细胞活性,下调细胞因子TNF-α的水平,从而对EAE具有保护作用。Objective To observe the therapeutic effect of atorvastatin on experimental autoimmune encephalomyelitis （EAE） in SD rats and to explore its mechanisms. Methods The rat model of EAE was established by the use of isogenic cerebrospinal neat jelly and then atorvastatin was administered for interventional treatment. The clinical symptoms and pathological alterations were observed and analyzed. The responses of microglia to the inflammatory lesions were detected using immunohistochemistry, as were the TNF-α expressions in the cerebral tissues and the peripheral blood by immunohistochemistry and ELISA, respectively. Results Atorvastatin could relieve clinical symptoms, shorten course, reduce relapse rates, and alleviate inflammatory reaction and demyelination （P 〈 0.05）. There were significant differences between the atorvastatin group and the non-treatment group in the number of the cerebral microglia and TNF-α-positive cells and the peripheral TNF-α level at the peak stage of inflammation. Conclusion Atorvastatin plays a protective role in EAE by inhibiting the activity of microglia and downregulating the expression of TNF-α.

关 键 词：脑脊髓炎 自身免疫性 实验性 阿托伐他汀 小胶质细胞 

分 类 号：R96[医药卫生—药理学]