他汀类药物与血脑屏障

他汀类药物通过抑制羟甲基戊二酰辅酶A(HMG-CoA)还原酶,上调脑组织内皮型一氧化氮合酶(eNOS)的表达和活化,升高血清过氧化氢酶和血浆NO浓度,增强抗氧化能力,降低氧自由基含量,改善紧密连接的闭锁小带和跨膜蛋白以及星形胶质细胞的胶质纤维酸性蛋白的免疫反应性。他汀类药物还可能发挥与抑制HMG-CoA还原酶完全无关的效应,即与白细胞功能抗原-1的L位点结合,抑制其与细胞间黏附分子-1之间的相互作用,起到抗炎和免疫调节作用。以上机制均有助于保持病理情况下血脑屏障的完整性和星形胶质细胞的功能。

Statins and Blood-Brain Barrier

By inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, statins up-regulate the expression and activation of endothelial nitric oxide synthase (eNOS) in brain tissues, increase the levels of serum catalase and plasma nitric oxide, enhance antioxidant capacity, decrease oxygen free radical release, improve immunoreactivities of tight junction (zonula occludens), transmembrane proteins and glial fibrillary acidic protein of astrocyte. Stains may also exert the effects that is completely unrelated with inhibiting HMG-CoA reductase, e.g. binding to leucocyte function-associated antigen-1(LFA-1) L-site, restraining its interactions between LFA-1 and intercellular adhesion molecule-1 (ICAM-1), and playing anti-inflammation and immunoloregulation roles. The above mechanisms contribute to remain the integrity of blood-brain barrier and the activity of astrocyte under the pathological conditions.