Role Of TLR3Signaling Pathway In Neuroprotection Of Sevoflurane Preconditioning During Cardiopulmonary Bypass In Rats

Objective: To investigate the effect and molecular mechanism of TLR3signalingpathway plays in the neuroprotection of sevoflurane preconditioning duringcardiopulmonary bypass in rats.Methods: Male Sprague-Dawley rats were divided into3groups randomly: controlgroup (group H, n=8), CPB group (group C, n=24) and sevoflurane preconditioninggroup (group S, n=32). Group H: given mechanical ventilation after trachealintubation,punctured in the corresponding vascular, without CPB. Group C: puncturedthe right jugular vein and right femoral artery to establish the cardiopulmonary bypassmodel flushed without blood. Group S: preconditioned1h under2.4%sevoflurane, andestablished CPB model. Given group C and S CPB for1h. After anesthesia and beforeCPB (T0), CPB30min (T1), immediately after CPB1h (T2), stop CPB1h (T3), stopCPB2h (T4) and stop CPB3h (T5), blood samples were collected, vital signs wererecord. At T0, T1, T3and T5, killed8rats to get brains. Used ELISA to measure S100-β,IL–6and IFNβ in serum. Used ELISA to measure the expression level of TLR3andTRIF in the left hippocampus;Used Western Blot to test the expression level of TLR3in the left hippocampus; Used TUNEL to test neuron apoptosis in the righthippocampus.Results:MAP, HR, rectal temperature, pH value, BE values,PaCO2, PaO2, K+in three decreased（compared with T0，P<0.05）.Contrast group H, the serum concentrations of S100-β and IL-6both risen in groupC and group S（P<0.05）.The serum concentrations of S100-β and IL-6in group C and Swere significantly increased during CPB（P<0.05）. In group S, at T1~T5, the serumconcentrations of S100-β and IL-6were decreased contrast group C（P<0.05）.The serum concentrations of IFNβ in group C and S was significantly increased atT1~T5（compared with T0，P<0.05）. At each time point in group S, the serum IFNβwas increased except T0in contrast to group C（P<0.05）.Contrast group H, in the group C and group S,TLR3and TRIF expression weresignificantly increased（P<0.05）.In group C the expression of TLR3and TRIF wereincreased at T1, but decreased at T（3compared with T0，P<0.05）. Compared with groupH,during T1,T3,T5, the expression of TLR3and TRIF were increased in the group Cand group S（P<0.05）.In the western blot, the expression of TLR3, in Group C and S, were higher thangroup H. Contrast group C,Group S was higher（P<0.05）.In the TNNEL, hippocampal neuron apoptosis cells is few with Group H. Group Cand S compared with the group H, apoptosis cell increased（P<0.05）. Apoptosis cellswere decreased than group C in group S（P<0.05）.Conclusion:1.2.4%Sevoflurane preconditioning has neuroprotection in CPB brain injury.2. TLR3signaling pathway is activated by sevoflurane preconditioning. Up-regulatedits expression level to reduce the brain injury caused by CPB inflammation and thusits play a role of neuroprotection.3. TLR3signaling pathway play a role of neuroprotection in sevofluranepreconditioning. The possible mechanism:the sevoflurane activate TLR3inadvance, raised the creating of TRIF, restrain the release of the inflammatoryfactors IL-6, increase the expression of anti-inflammatory factor IFN-β, restraininflammatory caused by CPB.