Propofol alleviates spinal cord ischemia-reperfusion injury by preserving PI3K/AKT/GIT1 axis

• Published in: Journal of investigative medicine 2024-10, Vol.72 (7), p.705-714
• Main Authors: Zhou, Yilin, Bai, Yuyan, Zhang, Peisen, Weng, Peiqing, Xie, Wenxi
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Cell Cycle Proteins - metabolism; GTPase-Activating Proteins - metabolism; Male; Phosphatidylinositol 3-Kinases - metabolism; Propofol - pharmacology; Propofol - therapeutic use; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Sprague-Dawley; Reperfusion Injury - drug therapy; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Signal Transduction - drug effects; Spinal Cord - drug effects; Spinal Cord - metabolism; Spinal Cord - pathology; Spinal Cord Ischemia - drug therapy; Spinal Cord Ischemia - metabolism; Spinal Cord Ischemia - pathology
• ISSN: 1081-5589; 1708-8267; 1708-8267
• DOI: 10.1177/10815589241254044

Spinal cord ischemia-reperfusion injury (SCIRI) is a major contributor to neurological damage and mortality associated with spinal cord dysfunction. This study aims to explore the possible mechanism of Propofol and G-protein-coupled receptor-interacting protein 1 (GIT1) in regulating SCIRI in rat models. SCIRI rat models were established and injected with Propofol, over expression of GIT1 (OE-GIT1), or PI3K inhibitor (LY294002). The neurological function was assessed using Tarlov scoring system, and Hematoxylin & Eosin (H&E) staining was applied to observe morphology changes in spinal cord tissues. Cell apoptosis, blood-spinal cord barriers (BSCB) permeability, and inflammatory cytokines were determined by TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, evans blue (EB) staining, and enzyme-linked immuno sorbent assay (ELISA), respectively. Reverse transcription-quantitative polymerase chain reaction and western blot were used to detect the expression levels of GIT1, endothelial nitric oxide synthase (eNOS), PI3K/AKT signal pathway and apoptosis-related proteins. SCIRI rats had decreased expressions of GIT1 and PI3K/AKT-related proteins, whose expressions can be elevated in response to Propofol treatment. LY294002 can also decrease GIT1 expression levels in SCIRI rats. Propofol can attenuate neurological dysfunction induced by SCIRI, decrease spinal cord tissue injury and BSCB permeability in addition to suppressing cell apoptosis and inflammatory cytokines, whereas further treatment by LY294002 can partially reverse the protective effect of Propofol on SCIRI. Propofol can activate PI3K/AKT signal pathway to increase GIT1 expression level, thus attenuating SCIRI in rat models.