Human serum albumin attenuates global cerebral ischemia/reperfusion-induced brain injury in a Wnt/β-Catenin/ROS signaling-dependent manner in rats

作者：Yuedong Tang, Jie Shen, Feng Zhang, Feiyu Yang, Ming Liu · 发表于：Biomedicine & Pharmacotherapy · 年份：2019 · DOI：10.1016/j.biopha.2019.108871 · 被引用次数：34 · 研究领域：S100 Proteins and Annexins、Barrier Structure and Function Studies、Axon Guidance and Neuronal Signaling

This study sought to clarify the role and underlying mechanisms of human serum albumin (HSA) therapy in global cerebral ischemia/reperfusion (GCI/R)-induced brain damage in rats. Five groups of adult male Wistar rats (n = 12 per group) were created as follows: sham operation (Sham), global cerebral ischemia/reperfusion (GCI/R), HSA treatment (GCI/R + HSA), Dickkopf-1 (DDK1) treatment (GCI/R + DDK1), and DDK1 plus HSA treatment (GCI/R + DKK1 + HSA). The GCI/R injury model was created using the modified Pusinelli four-vessel occlusion method. After 24 h, rats were evaluated using neurological scoring, Nissl staining, and brain tissue water content. The mRNA expression of Wnt, GSK3β, and β-Catenin in the brain were detected by quantitative real time polymerase chain reaction. The protein expression of β-Catenin and GSK-3β were investigated by western blot and immunohistochemical analysis in the presence and absence of the Wnt/β-Catenin antagonist, DKK-1. Complex I activity and ROS content were also measured. After 24 h of reperfusion, the behavior score and brain tissue water content in the GCI/R + HSA group were lower than that in the GCI/R group. In addition, the degree of neuronal injury was significantly reduced in the GCI/R + HSA group (P < 0.05). The ROS content was significantly decreased and Complex I activity was markedly raised in the GCI/R + HSA group compared to the GCI/R group (P < 0.05). Further, GSK-3β expression in the GCI/R + HSA group was lower than that in the...