Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education and Ministry of Public Health, Health Science Center, Peking University, Beijing, China.
Center of Medical and Health Analysis, Peking University, Beijing, China.
Biochem Biophys Res Commun. 2014 Mar 7;445(2):352-6. doi: 10.1016/j.bbrc.2014.01.194. Epub 2014 Feb 7.
Phospholipid transfer protein (PLTP) regulates lipid metabolism and plays an important role in oxidative stress. PLTP is highly expressed in blood-brain barrier (BBB), but the role of PLTP in BBB integrity is not clear. In this study, BBB permeability was detected with in vivo multiphoton imaging and Evans blue assay. We found that PLTP deficient mice exhibited increased BBB permeability, as well as decreased expression of tight junction proteins occludin, zona occludens-1 (ZO-1) and claudin-5 in brain vessels. Cerebrovascular oxidative stress increased in PLTP deficient mice, including increased levels of reactive oxygen species (ROS) and lipid peroxidation marker 4-hydroxy-2-nonenal (HNE) and reduced superoxide dismutase (SOD) activity. Dietary supplementation of antioxidant vitamin E increased BBB integrity and tight junction proteins expression via reducing cerebrovascular oxidative stress. These findings indicated an essential role of PLTP in maintaining BBB integrity, possibly through its ability to transfer vitamin E, and modulate cerebrovascular oxidative stress.
磷脂转移蛋白（PLTP）调节脂质代谢，在氧化应激中发挥重要作用。PLTP 在血脑屏障（BBB）中高度表达，但 PLTP 在 BBB 完整性中的作用尚不清楚。在这项研究中，通过体内多光子成像和 Evans 蓝测定检测 BBB 通透性。我们发现 PLTP 缺陷小鼠表现出 BBB 通透性增加，以及脑血管中紧密连接蛋白 occludin、zonula occludens-1 (ZO-1) 和 claudin-5 的表达减少。PLTP 缺陷小鼠脑血管氧化应激增加，包括活性氧 (ROS) 和脂质过氧化标志物 4-羟基-2-壬烯醛 (HNE) 水平升高，以及超氧化物歧化酶 (SOD) 活性降低。抗氧化维生素 E 的膳食补充通过减少脑血管氧化应激增加了 BBB 的完整性和紧密连接蛋白的表达。这些发现表明 PLTP 在维持 BBB 完整性方面起着重要作用，可能是通过其转移维生素 E 的能力，并调节脑血管氧化应激。
