Effects of TLR3 and TLR9 Signaling Pathway on Brain Protection in Rats Undergoing Sevoflurane Pretreatment during Cardiopulmonary Bypass.

OBJECTIVE:To investigate the effects of TLR3 and TLR9 signaling pathway on brain injury during CPB in rats pretreated with sevoflurane and its possible molecular mechanism. METHODS:SD rats were randomly assigned to sham group, CPB group, and Sev group. Brain tissue was obtained at before CPB (T₀), at CPB for 30 minutes (T₁), 1 hour after CPB (T₃), and 3 hours after CPB (T₅). ELISA was used to measure S100-β and IL-6. Western blot was utilized to determine TLR3 and TLR9 expression. TUNEL was applied to detect neuronal apoptosis. RESULTS:Compared with CPB group, at T₁, at termination after 1 hour of CPB (T₂), T₃, 2 hours after CPB (T₄) and T₅, S100-β and IL-6 decreased in Sev group. Compared with CPB group, IFN-β were increased in Sev group, except T₀. Compared with CPB group, TLR3 expression increased, and TLR9 and NF-κB decreased in Sev group. The apoptotic neurons were less in Sev group than in CPB group (P < 0.05). CONCLUSION:Sevoflurane intervention can activate TLR3 and TLR9 signaling pathway, upregulate TLR3 expression and downstream TRIF expression, decrease TLR9 expression, and downregulate downstream NF-κB expression in CPB rat models, thereby mitigating brain injury induced by inflammatory response during CPB.

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