Role of Toll-like receptor 4 signaling pathway in sevoflurane anesthesia-induced cognitive dysfunction in aged rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of Toll-like receptor 4 (TLR4) signaling pathway in sevoflurane anesthesia-induced cognitive dysfunction in aged rats.Methods Twenty-seven SPF healthy male Sprague-Dawley rats,aged 20 months,weighing 550-750 g,were divided into 3 groups (n =9 each) using a random number tablecontrol group (C group),sevoflurane anesthesia group (S group) and TLR4 antagonist plus sevoflurane anesthesia group (TS group).TLR4 monoclonal antibody 30 μl was injected into the lateral cerebral ventricle in group TS,and the equal volume of serum containing no antibody was injected into the lateral cerebral ventricle in C and S groups.At 10 min after completion of injection,S and TS groups inhaled the mixture of 4％ sevoflurane and 30％ oxygen for 6 h,and group C only inhaled the mixture of air and oxygen.Morris water maze test was performed at 24 h after the end of sevoflurane anesthesia.The animals were sacrificed after completion of Morris water maze test,brains were removed and hippocampi were isolated for determination of nerve cell apoptosis (using TUNEL) and expression of activated caspase-3 (using immunofluorescent staining).Nerve cell apoptosis rate was calculated.The expression of high-mobility group box 1 protein (HMGB1) mRNA in hippocampi was measured by Northern blot assay at 6 h after the end of sevoflurane anesthesia.The expression of amyloid precursor protein (APP) and amyloid beta protein (Aβ) in hippocampi was assessed by Western blot at 24 h after the end of sevoflurane anesthesia.Results Compared with C group,the escape latency was significantly prolonged,nerve cell apoptosis rate was increased,the expression of activated caspase-3,HMGB1 mRNA,APP and Aβ was up-regulated in group S,and nerve cell apoptosis rate was increased,the expression of activated caspase-3,HMGB1 mRNA,APP and Aβ was up-regulated (P＜0.05),and no significant change was found in the escape latency in group TS (P＞0.05).Compared with S group,the escape latency was significantly shortened,nerve cell apoptosis rate was decreased,and the expression of activated caspase-3,HMGB1 mRNA,APP and Aβ was down-regulated in group TS (P＜0.05).Conclusion Activation of TLR4 signaling pathway is involved in the mechanism of sevoflurane anesthesia-induced cognitive dysfunction in aged rats.