Role of nuclear factor kappa B in cognitive decline in aged mice with sepsis / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of nuclear factor kappa B (NF-κB) in cognitive decline in aged mice with sepsis.Methods Forty-five SPF healthy aged female C57BL/6 mice,aged 10-12 months,weighing 20-30 g,were assigned into 3 groups (n=15 each) using a random number tablecontrol group (group C),sepsis group (group Sep) and NF-κB selective inhibitor pyrrolidine dithiocarbamate (PDTC) group (group PDTC).Lipopolysaccharide 250 μg/kg was injected intraperitoneally once a day for 7 consecutive days in Sep and PDTC groups,and in addition PDTC 50 mg/kg was injected intraperitoneally at 30 min before lipopolysaccharide injection once a day for 7 consecutive days in group PDTC.The equal volume of normal saline was given in group C.Five mice in each group were sacrificed at 2 h after the last administration,cardiac puncture was performed and blood samples were collected,and then the mice were sacrificed and hippocampi were harvested for determination of the levels of tumor necrosis factor-α (TNF-α),interleukin-1β (IL-1β) and IL-6 in plasma and hippocampal tissues using enzyme-linked immunosorbent assay.Cognitive function was assessed using open field,elevated plus maze and Morris water maze tests at 24 h after the last administration in the other mice left in each group.Results Compared with group C,the levels of TNF-α,IL-1β and IL-6 in plasma and hippocampal tissues were significantly increased,the time of movement at the central region was shortened,the percentage of time spent in the open arms and number of entries into the open and closed arms were decreased,the escape latency was prolonged,the time of staying at the original platform quadrant was shortened,and the frequency of crossing the platform was decreased in group Sep (P＜0.05).Compared with group Sep,the levels of TNF-α,IL-1β5 and IL-6 in plasma and hippocampal tissues were significantly decreased,the time of movement at the central region was prolonged,the percentage of time spent in the open arms and number of entries into the open and closed arms were increased,the escape latency was shortened,and the time of staying at the original platform quadrant was prolonged in group PDTC (P＜0.05).Conclusion NF-κB is involved in cognitive decline in aged mice with sepsis.