关键词: 瑞马唑仑, 创伤性脑损伤, 神经保护

Abstract: Objective To explore the neuro-protective effect of remimazolam (Rem) on traumatic brain injury (TBI) in rat models. Methods A TBI rat model was constructed. The rats were randomly divided into control group, traumatic brain injury group (TBI group), low-dose and high-dose remimazolam groups (Rem-L, Rem-H groups), and high-dose remimazolam+Jagged1 group (Rem-H+Jagged1 group), with 12 rats in each. All rats were evaluated for neurological deficits. The serum level of inflammatory factors like tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) were detected by ELISA. HE staining microscopy was used to observe the changes of brain histopathology. The expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptation molecule 1 (IBA1) were detected by immunohistochemistry. Western blot was applied to detect the expression of Notch, Notch 1 intracellular domain (NICD) and Hes-1 protein in the brain tissue. Results Compared with the control group, the TBI group showed a larger area of brain tissue defect and edema, with more activated glial cells and fragmented, concentrated and deeply stained neuronal nuclei, indistinct nucleoli, deeply stained cytoplasm, and partial neuronal necrosis The neurological deficit score was higher, level of TNF-α and IL-1β and the expression of GFAP, IBA1, Notch, NICD, and Hes-1 all elevated (P＜0.05). Remazolam reduced brain tissue defect area, alleviated edema, inhibited glial cell activation and neuronal apoptosis, and reduced nerve function deficit score, the level of TNF-α and IL-1β, and the expression of GFAP, IBA1, Notch, NICD and Hes-1(P＜0.05). Jagged1 could aggravate brain tissue injury, increase neural function deficit score, levels of TNF-α and IL-1β and expressions of GFAP, IBA1, Notch, NICD and Hes-1 (P＜0.05). Conclusions Remimazolam may have neuroprotective effects as shown by TBI rat models, and the underlying mechanism is potentially related to the inhibition of the Notch/Hes-1 signaling pathway.

Key words: remimazolam, traumatic brain injury, neuroprotection