Role of hippocampal ApoE in age factors-induced effect on long-term cognitive function in mice undergoing multiple exposure to sevoflurane anesthesia: gene knockout method / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of hippocampal ApoE in age factors-induced effect on long-term cognitive function in mice undergoing multiple exposure to sevoflurane anesthesia using the gene knockout method.Methods:Seventy-two juvenile (6 days old, weighing 3-5 g) and adult (60 days old, weighing 20-25 g) wild-type (WT) C57BL/6J mice and 56 ApoE gene knockout (ApoE-KO) C57BL/6J mice were studied.WT mice were divided into 4 groups ( n=18 each) using a random number table method: juvenile control group (P6+ C group), juvenile sevoflurane group (P6+ S group), adult control group (P60+ C group) and adult sevoflurane group (P60+ S group). ApoE-KO mice were randomly divided into 4 groups ( n=14 each) according to a random number table method: juvenile control group (P6+ C group), juvenile sevoflurane group (P6+ S group), adult control group (P60+ C group) and adult sevoflurane group (P60+ S group). Mice inhaled 3% sevoflurane in 60% O 2 for 2 h every day for 3 consecutive days in sevoflurane group, while mice were placed in the same environment and inhaled 60% O 2 for 2 h every day for 3 consecutive days in control group.Four mice were selected at the end of sevoflurane anesthesia (8 or 62 days after birth) for determination of IL-1β, IL-6 and TNF-α contents in hippocampus by enzyme-linked immunosorbent assay.Four mice in each group of WT mice were randomly selected to detect the expression of full-length ApoE and ApoE fragments in hippocampus by Western blot.The remaining 10 mice in each group of WT mice received standardized feeding, and contextual fear conditioning test was performed at 22 days after sevoflurane anesthesia (30 or 84 days after birth). Results:WT mice Compared with P6+ C group, IL-1β, IL-6 and TNF-α contents were significantly increased, the expression of full-length ApoE and ApoE fragments was up-regulated, and the standstill time was shortened in P6+ S group ( P <0.05), and no significant change was found in the parameters mentioned above in P60+ C and P60+ S groups ( P>0.05). ApoE-KO mice Compared with P6+ C and P6+ S groups, no significant change was found in IL-1β, IL-6 and TNF-α contents or standstill time in P60+ C group and P60+ S group ( P>0.05). Conclusion:The mechanism of age influencing the long-term cognitive dysfunction is related to up-regulating ApoE expression in hippocampus and inducing neuroinflammatory response in mice undergoing multiple exposure to sevoflurane anesthesia.