Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Beijing Key Laboratory of Hypoxia Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.
J Cereb Blood Flow Metab. 2021 Jun;41(6):1277-1290. doi: 10.1177/0271678X20952264. Epub 2020 Sep 15.
Oxygen supply for ischemic brain tissue during stroke is critical to neuroprotection. Remote ischemic conditioning (RIC) treatment is effective for stroke. However, it is not known whether RIC can improve brain tissue oxygen supply. In current study, we employed a mouse model of stroke created by middle cerebral artery occlusion (MCAO) to investigate the effect of RIC on oxygen supply to the ischemic brain tissue using a hypoxyprobe system. Erythrocyte oxygen-carrying capacity and tissue oxygen exchange were assessed by measuring oxygenated hemoglobin and oxygen dissociation curve. We found that RIC significantly mitigated hypoxic signals and decreased neural cell death, thereby preserving neurological functions. The tissue oxygen exchange was markedly enhanced, along with the elevated hemoglobin P50 and right-shifted oxygen dissociation curve. Intriguingly, RIC markedly elevated 2,3-biphosphoglycerate (2,3-BPG) levels in erythrocyte, and the erythrocyte 2,3-BPG levels were highly negatively correlated with the hypoxia in the ischemic brain tissue. Further, adoptive transfusion of 2,3-BPG-rich erythrocytes prepared from RIC-treated mice significantly enhanced the oxygen supply to the ischemic tissue in MCAO mouse model. Collectively, RIC protects against ischemic stroke through improving oxygen supply to the ischemic brain tissue where the enhanced tissue oxygen delivery and exchange by RIC-induced 2,3-BPG-rich erythrocytes may play a role.
脑缺血组织的氧供对于神经保护至关重要。远程缺血预处理（RIC）治疗对中风有效。然而，尚不清楚 RIC 是否能改善脑组织的氧供。在本研究中，我们采用大脑中动脉闭塞（MCAO）所致的中风小鼠模型，利用缺氧探针系统研究 RIC 对缺血脑组织氧供的影响。通过测量氧合血红蛋白和氧离曲线评估红细胞携氧能力和组织氧交换。我们发现 RIC 显著减轻了缺氧信号，减少了神经细胞死亡，从而保护了神经功能。组织氧交换明显增强，血红蛋白 P50 升高，氧离曲线右移。有趣的是，RIC 显著提高了红细胞中的 2,3-二磷酸甘油酸（2,3-BPG）水平，而红细胞中的 2,3-BPG 水平与缺血脑组织中的缺氧高度负相关。此外，从 RIC 处理的小鼠中制备的富含 2,3-BPG 的红细胞过继输注显著增强了 MCAO 小鼠模型中缺血组织的氧供。总之，RIC 通过改善缺血脑组织的氧供来预防缺血性中风，RIC 诱导的富含 2,3-BPG 的红细胞可能通过增强组织氧输送和交换来发挥作用。
