Fujimoto Takashi, Morofuji Yoichi, Kovac Andrej, Erickson Michelle A, Deli Mária A, Niwa Masami, Banks William A
Department of Neurosurgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Division of Gerontology and Geriatric Medicine, Department of Medicine, School of Medicine, University of Washington, Seattle, WA 98108, USA.
Biomedicines. 2021 Jul 18;9(7):837. doi: 10.3390/biomedicines9070837.
Statins have neuroprotective effects on neurological diseases, including a pleiotropic effect possibly related to blood-brain barrier (BBB) function. In this study, we investigated the effects of pitavastatin (PTV) on lipopolysaccharide (LPS)-induced BBB dysfunction in an in vitro BBB model comprising cocultured primary mouse brain endothelial cells, pericytes, and astrocytes. LPS (1 ng/mL, 24 h) increased the permeability and lowered the transendothelial electrical resistance of the BBB, and the co-administration of PTV prevented these effects. LPS increased the release of interleukin-6, granulocyte colony-stimulating factor, keratinocyte-derived chemokine, monocyte chemotactic protein-1, and regulated on activation, normal T-cell expressed and secreted from the BBB model. PTV inhibited the LPS-induced release of these cytokines. These results suggest that PTV can ameliorate LPS-induced BBB dysfunction, and these effects might be mediated through the inhibition of LPS-induced cytokine production. Clinically, therapeutic approaches using statins combined with novel strategies need to be designed. Our present finding sheds light on the pharmacological significance of statins in the treatment of central nervous system diseases.
他汀类药物对神经疾病具有神经保护作用，包括可能与血脑屏障（BBB）功能相关的多效性作用。在本研究中，我们在一个由原代小鼠脑内皮细胞、周细胞和星形胶质细胞共培养组成的体外血脑屏障模型中，研究了匹伐他汀（PTV）对脂多糖（LPS）诱导的血脑屏障功能障碍的影响。LPS（1 ng/mL，24小时）增加了血脑屏障的通透性并降低了跨内皮电阻，而PTV的共同给药可防止这些作用。LPS增加了白细胞介素-6、粒细胞集落刺激因子、角质形成细胞衍生趋化因子、单核细胞趋化蛋白-1的释放，并调节了血脑屏障模型中活化正常T细胞表达和分泌的物质。PTV抑制了LPS诱导的这些细胞因子的释放。这些结果表明，PTV可以改善LPS诱导的血脑屏障功能障碍，并且这些作用可能是通过抑制LPS诱导的细胞因子产生来介导的。临床上，需要设计将他汀类药物与新策略相结合的治疗方法。我们目前的发现揭示了他汀类药物在中枢神经系统疾病治疗中的药理学意义。
