Weber Martin S, Steinman Lawrence, Zamvil Scott S
Department of Neurology and Program in Immunology, University of California, San Francisco, California 94143, USA.
Neurotherapeutics. 2007 Oct;4(4):693-700. doi: 10.1016/j.nurt.2007.08.004.
Statins, inhibitors of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase, are well-established agents to lower cholesterol levels and prevent cardiovascular morbidity. Independent of their lipid-lowering properties, statins have been shown to exert pleiotropic immunomodulatory effects in various animal models of human autoimmune disease. In experimental autoimmune encephalomyelitis, a murine model for multiple sclerosis, statins prevented disease onset and even reversed paralysis when treatment was initiated after experimental autoimmune encephalomyelitis was fully established. Furthermore, well-tolerated oral statins were recently shown to exert synergistic benefit in experimental autoimmune encephalomyelitis in combination with existing agents for multiple sclerosis therapy. Based primarily on these encouraging results, statins are now being tested in clinical trials as a monotherapy for multiple sclerosis, as well as in combination with approved disease-modifying therapies.
他汀类药物是3-羟基-3-甲基戊二酰辅酶A还原酶的抑制剂,是降低胆固醇水平和预防心血管疾病的成熟药物。除了其降脂特性外,他汀类药物已被证明在多种人类自身免疫性疾病的动物模型中发挥多效性免疫调节作用。在实验性自身免疫性脑脊髓炎(一种多发性硬化症的小鼠模型)中,他汀类药物可预防疾病发作,甚至在实验性自身免疫性脑脊髓炎完全形成后开始治疗时可使瘫痪逆转。此外,最近研究表明,耐受性良好的口服他汀类药物与现有的多发性硬化症治疗药物联合使用时,在实验性自身免疫性脑脊髓炎中具有协同益处。主要基于这些令人鼓舞的结果,他汀类药物目前正在临床试验中作为多发性硬化症的单一疗法以及与已批准的疾病改善疗法联合使用进行测试。