Effects of Remimazolam on Brain Tissue Injury and TLR4/MyD88/NF-κB Pathway in Rats with Traumatic Brain Injury
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 vol-ume decreased,and the injury was serious.Neural function score,brain tissue water content,neuronal apop-tosis 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 suc-cessively,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 in-hibiting the TLR4/MyD88/NF-κB pathway.