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Effects of Remimazolam on Brain Tissue Injury and TLR4/MyD88/NF-κB Pathway in Rats with Traumatic Brain Injury |
WANG Dongya, QIAO Dan, CHEN Weijia, et al |
No.2 Hospital of Baoding, Hebei Baoding 071000, China |
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Abstract Objective: To investigate the effects of Remimazolam on brain tissue injury and the Toll like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) pathway in rats with traumatic brain injury (BI). Methods: BI rat model was constructed; All rats were grouped into Control group, brain injury group (BI group), low, medium and high dose Remimazolam groups (Rem-L, Rem-M, Rem-H groups), and high dose Remimazolam+TLR4 activator LPS group of (Rem-H+LPS group); the brain tissue water content was detected; ELISA was applied to detect the levels of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in rat brain tissue; HE staining was applied to observe the morphological changes of brain tissue; TUNEL method was applied to detect neuronal apoptosis in brain tissue; Western blot method was applied to detect the expression of TLR4, MyD88, NF-κB, p-NF-κB p65, Bax, and Bcl-2 proteins in brain tissue. Results: Compared with Control group, brain neurons in BI group were degenerated and necrotic, the number of neurons decreased, the volume decreased, and the injury was serious. Neural function score, brain tissue water content, neuronal apoptosis rate, levels of TNF-α, IL-1β, IL-6 and expressions of Bax, TLR4, MyD88, NF-κB, p-NF-κB p65 were increased. Bcl-2 expression decreased (P<0.05); Compared with BI group, the neuronal cell damage in brain tissue of rats in Rem-L, Rem-M and Rem-H groups was gradually reduced, and the cell structure was relatively clear. The neural function score, brain tissue water content, neuronal apoptosis rate, TNF-α, IL-1β, IL-6 levels and the expressions of Bax, TLR4, MyD88, NF-κB, p-NF-κB p65 were decreased successively, while the expression of Bcl-2 was increased successively (P<0.05); Compared with the Rem-H group, the brain tissue injury of the rats in the Rem-H+LPS group was aggravated, the neural function score, brain tissue water content, neuronal apoptosis rate, the levels of TNF-α, IL-1β, IL-6 and the expressions of Bax, TLR4, MyD88, NF-κB, p-NF-κB p65 were increased, and the expression of Bcl-2 was decreased (P<0.05). Conclusion: Remimazolam can improve brain tissue injury in rats with traumatic brain injury by inhibiting the TLR4/MyD88/NF-κB pathway.
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