The Effect Of Different Concentration Of Sevoflurane Preconditioning On The Brain Ischemic And TLR9Signaling Pathway On Rat Cardiopulmonary Bypass

Objective:To explore the neuroprotection of sevoflurane preconditioning for ischemic brain andthe impact on the expression of TLR9signaling pathway with a rat model ofcardiopulmonary bypass.Methods:Forty male SD rats weighting of350g~450g were randomly divided into5groups (n=8): sham operated group (group H): just punctured tube didn’t establish CPB model;cardiopulmonary bypass group (group C): punctured tube and established CPB model;sevoflurane preconditioning group (group S): S1, S2, and S3group respectively in ahomemade container with1.2%,2.4%and3.6%sevoflurane pretreatment,and thenestablished CPB model.The model of cardiopulmonary bypass is established by rightjugular vein drainage and right femoral artery perfusion，and maintains60min. Groupset up six points: T0(after pretreatment, before transferring), T1(CPB30min), T2(CPB1h), T3(1h after CPB), T4(2h after CPB) and T5(3h after CPB). ELISAmethod to detect serum S100-β and NF-κB concentration at each time point.Hippocampus neuron apoptosis tested by TUNEL method at3h after the CPB,calculated the Integrated OD Average;Western blotting method to detect brain tissueTLR9protein expression levels. Results:1.The analysis results of CPB group rats with the time point of the MAP, HR, RectalTemperature and blood gasMAP、HR significantly lower after began to bypass (compared with T0, P <0.05),and restore the original level when CPB1h (compared with T0, P>0.05);T ismatains32℃~34℃during CPB; pH is stability during CPB; PaCO2、PaO2isrelatively stable before and after CPB (compared with T0，P>0.05);Hct decreasesobviously due to the hemodilution during CPB (P <0.05); K+levels remaines stableduring CPB (compared with T0，P>0.05).2.TUNEL method in detection hippocampal neuron apoptosisCompared with the H group, IA value of C and S1~S3groups is increased(P <0.05);Compared with C group, IA value of S1~S3groups is relatively lower (P <0.05);Compared with S1group, IA value of S2and S3groups is relatively lower (P <0.05);Compared with S2group, IAvalue of S3group is relatively lower (P <0.05).3.The ELISAassay results of different time points serum S100-β in each groupCompared with the T0, the serum S100-β of C and S1~S3groups is elevated at thetime of T1~5(P <0.05). During the time of T1~T5:compared with the H group, theserum S100-β of C and S1~S3groups is elevated (P <0.05);compared with C group,the serum S100-β of S1~S3group is relatively lower (P <0.05);compared with S1group, the serum S100-β of S2and S3groups is relatively lower (P <0.05);comparedwith S2group, the serum S100-β of the group S3is relatively lower (P <0.05)4.The ELISAassay results of different time points serum NF-κB in each groupCompared with the T0, the serum NF-κB of C and S1~S3groups is elevated at thetime of T1~5(P <0.05). During the time of T1~T5:compared with the H group, theserum NF-κB of C and S1~S3groups is elevated (P <0.05);compared with C group,the serum NF-κB of S1~S3group is relatively lower (P <0.05);compared with S1group, the serum NF-κB of S2and S3groups is relatively lower (P <0.05);comparedwith S2group, the serum NF-κB of the group S3is relatively lower (P <0.05)5.Western blot results of brain tissue expression of TLR9in each groupCompared with the H group, expression of TLR9of C and S1~S3groups isupregulated(P <0.05);compared with C group, expression of TLR9of S1~S3groups is relatively lower (P <0.05);compared with S1group, expression of TLR9of S2andS3groups is relatively lower (P <0.05);compared with S2group, expression of TLR9of S3group is relatively lower (P <0.05)Conclusins:1. TLR9singling pathway may mediates the development of ischemic brain injurycaused by cardiopulmonary bypass with rats.2. Sevoflurane preconditioning has the neuroprotection for ischemic brain damagethough deseases the TLR9/NF-κB inflammanaty singling pathway,and have a dosedependent with a certain range.