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Biomed Pharmacother. 2019 Jul;115:108871. doi: 10.1016/j.biopha.2019.108871. Epub 2019 Apr 23.

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

Author information

1
Department of Emergency and Critical Care Medicine, Jinshan Hospital, Fudan University, Shanghai, China; Medical Center of Chemical Injury, Emergency and Critical Care, Jinshan Hospital, Fudan University, Shanghai, China; Medical Research Centre for Chemical Injury, Emergency and Critical Care, Fudan University, Shanghai, China.
2
Department of Emergency and Critical Care Medicine, Jinshan Hospital, Fudan University, Shanghai, China; Medical Center of Chemical Injury, Emergency and Critical Care, Jinshan Hospital, Fudan University, Shanghai, China; Medical Research Centre for Chemical Injury, Emergency and Critical Care, Fudan University, Shanghai, China. Electronic address: 578731124@qq.com.
3
Department of Respiration, Shanghai Punan Hospital, Shanghai, China.

Abstract

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 GCI/R group, while the Wnt and β-catenin expression were increased. These effects were reversed by DKK1. Taken together, we showed that HSA attenuates GCI/R-induced brain damage and may be neuroprotective via regulation of the Wnt/β-catenin/ROS signaling pathway.

KEYWORDS:

Global cerebral ischemia; Human serum albumin; Reactive oxygen species; Wnt; β-Catenin

PMID:
31026729
DOI:
10.1016/j.biopha.2019.108871
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