Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1148, Bichat-Claude Bernard Hospital, Paris University, 75018 Paris, France.
Department of Anesthesiology and Critical Care, Bichat-Claude Bernard Hospital, AP-HP. Nord, Paris University, 75018 Paris, France.
Int J Mol Sci. 2020 Dec 24;22(1):106. doi: 10.3390/ijms22010106.
High-density lipoproteins (HDLs) display endothelial protective effects. We tested the role of SR-BI, an HDL receptor expressed by endothelial cells, in the neuroprotective effects of HDLs using an experimental model of acute ischemic stroke. After transient intraluminal middle cerebral artery occlusion (tMCAO), control and endothelial SR-BI deficient mice were intravenously injected by HDLs or saline. Infarct volume and blood-brain barrier (BBB) breakdown were assessed 24 h post tMCAO. The potential of HDLs and the role of SR-BI to maintain the BBB integrity was assessed by using a human cellular model of BBB (hCMEC/D3 cell line) subjected to oxygen-glucose deprivation (OGD). HDL therapy limited the infarct volume and the BBB leakage in control mice relative to saline injection. Interestingly, these neuroprotective effects were thwarted by the deletion of SR-BI in endothelial cells and preserved in mice deficient for SR-BI in myeloid cells. In vitro studies revealed that HDLs can preserve the integrity of the BBB in OGD conditions, and that this effect was reduced by the SR-BI inhibitor, BLT-1. The protection of BBB integrity plays a pivotal role in HDL therapy of acute ischemic stroke. Our results show that this effect is partially mediated by the HDL receptor, SR-BI expressed by endothelial cells.
高密度脂蛋白（HDL）具有保护血管内皮的作用。我们利用短暂性大脑中动脉阻塞（tMCAO）的实验模型，检测了内皮细胞表达的 HDL 受体 SR-BI 在 HDL 的神经保护作用中的作用。tMCAO 后，通过静脉注射 HDL 或生理盐水，分别对对照组和内皮细胞 SR-BI 缺陷型小鼠进行处理。tMCAO 后 24 小时，评估梗死体积和血脑屏障（BBB）的破坏程度。利用体外 BBB 细胞模型（hCMEC/D3 细胞系）进行氧葡萄糖剥夺（OGD），评估 HDL 和 SR-BI 维持 BBB 完整性的潜力。与生理盐水注射相比，HDL 治疗可减少对照组小鼠的梗死体积和 BBB 渗漏。有趣的是，内皮细胞中 SR-BI 的缺失会阻碍这些神经保护作用，但在骨髓细胞中缺乏 SR-BI 的小鼠中，这种作用得以保留。体外研究显示，HDL 可在 OGD 条件下维持 BBB 的完整性，而 SR-BI 抑制剂 BLT-1 则降低了这一作用。BBB 完整性的保护在急性缺血性脑卒中的 HDL 治疗中起着关键作用。我们的结果表明，这种作用部分是由内皮细胞表达的 HDL 受体 SR-BI 介导的。
