The Effect Of Dexmedetomidine On TLR4 Expression Of Rat Hippocampal Injury By Cardiopulmonary Bypass

Objective:To explore the effect and molecular mechanism of dexmedetomidine on TLR4 expression of rat hippocampal injury by cardiopulmonary bypass.Methods:Sixty-four male Sprague-Dawley rats weighting of 350g~450g were randomly divided into 4 groups(n=16).Then,according to each set point in time,each time point 4.Sham operation group(Sham group): after anesthesia,rat tracheal intubation,the right internal jugular vein and the right femoral vein and left femoral artery and tail artery catheterization,without cardiopulmonary bypass.Extracorporeal circulation group(group CPB): CPB1 h,after intubation and arteriovenous puncture like Sham group.Dexmedetomidine pretreatment group(Dex group): rats by intraperitoneal injection of dexmedetomidine 50ug/kg,the rest of the Sham group.Dexmedetomidine group +CPB(DC group): rats by intraperitoneal injection of dexmedetomidine 50ug/kg,the rest of the CPB group.Each set of 4 time points: T1(pre CPB),T2(1H),T3(after 2 hours),T4(after 6 hours).Before the rats were sacrificed at each time point,venous blood was collected and serum was recovered after centrifugation.The concentration of S100-,IL-1 and TNF-were detected by enzyme-linked immunosorbent assay.In the end,the hippocampus was isolated and TUNEL method was used to detect the apoptosis of neurons in the hippocampus.Blot Western method was used to detect the expression of TLR4 and NF-k B,and the TLR4 protein was detected by immunohistochemistry.Results:1.TUNEL method for the determination of neuronal apoptosis in the hippocampusCompared with the Sham group,CPB group and DC group had higher IA value(p<0.05),suggesting that there was a significant apoptosis,and there was no significant difference between the IA group and the Sham group(p>0.05).2.ELISA enzyme linked immunosorbent assay to detect the concentration of S100-,IL-6 and TNF-αCompared with the Sham group,the serum levels of S100-β,IL-6,TNF-α and T2~T4 in CPB group and DC group were Dou Shenggao(p<0.05),and the concentration of S100-β,IL-6,and TNF-α in Dex group were not significantly changed(p>0.05);Compared with CPB group,the concentration of S100-β,IL-6,TNF-α and in serum of T2~T4group were decreased(p<0.05)at DC time.In the CPB group and DC group,compared with the T1 time,the serum levels of S100-β,IL-6,TNF-α and P<0.05 were increased(T2~T4).3.Effect of Dex on the expression of TLR4 and NF-κBp65 protein in the hippocampus after CPBCompared with the Sham group,the TLR4 and NF-κBp65 protein expression increased(p<0.05)in the CPB group and the DC group at T4 time point,and decreased the expression of TLR4 and NF-κBp65 in the Dex group at the same time(p<0.05);Comparison of the CPB group,the T4 in the DC group of TLR4 and NF κB p65 protein expression decreased(p<0.05),suggesting that dexmedetomidine can reduce the expression of TLR4 and NF-κB protein.Conclusins:1.TLR4 signaling pathway participates in the development of brain injury in CPB.2.Dexmedetomidine through inhibition of TLR4 signaling pathway,reduced the expression of the downstream of IL-6,the level of TNF-α and NF-κBp65 protein,and thus play a protective role in the brain.