Effect of dexmedetomidine on propofol-induced remote learning memory impairment in developing rats and mechanism
Objective To investigate whether dexmedetomidine(Dex)can modulate the effect of protein kinase A(PKA)on the improvement of propofol-induced learning memory function and the effect on hippocampal pyroptosis in developing rats.Meth-ods According to the random number table method,120 7-day-old SD rats were divided into six groups(n=20):a control(Con)group,a propofol(Pro)group,a Dex group,a Dex pre-administration(DP)group,a PKA specific antagonist(H89)+DP(HDP)group,and a di-methyl sulfoxide(DMSO)+DP(CDP)group.Rats in the Pro group were intraperitoneally injected with 50 mg/kg of propofol,followed by additional administration of 50 mg/kg propofol after the recovery of righting reflex(40-60 min).The Con group was intraperitoneally injected with an equal amount of normal saline.The Dex group was intraperitoneally injected with 25 μg/kg of Dex.The DP group was intraperitoneally injected with 25 μg/kg of Dex,followed by the same administration regimen with the Pro group 20 min later.Both the HDP group and the CDP group were intraperitoneally injected with 0.05 mg/kg of H89 and DMSO at 0.1 ml,respectively,followed by the same administration regimen with the DP group 1 h later.The rats were raised in the same litter until 30 d of age.Then,the Morris water maze was used to detect the prolonged escape latency and the number of platform crossings.The levels of hippocampal phosphorylated-PKA(p-PKA),nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor 3(NLRP3),cas-pase-1,and gasdermin-D protein(GSDMD)protein were detected by Western blot,while the lactate dehydrogenase(LDH)kit was uti-lized to detect hippocampal LDH concentrations.Results Compared with the Con group,the Pro,DP,HDP,and CDP groups showed prolonged escape latency,with a decreased number of platform crossings on days 2-4(all P＜0.05);the levels of hippocampal p-PKA protein decreased,while the levels of NLRP3,caspase-1,and GSDMD protein and LDH concentrations increased(all P＜0.05).Compared with the Pro group,the Dex,DP,and CDP groups presented shortened escape latency,with an increasing number of platform crossing on days 2-4(all P＜0.05);the levels of hippocampal p-PKA protein increased,while the levels of NLRP3,caspase-1,and GSD-MD protein and LDH concentrations decreased(all P＜0.05).Compared with the DP and CDP groups,the HDP group showed prolonged escape latency,with a reduced number of platform crossings on days 2-4(all P＜0.05);the levels of hippocampal p-PKA protein de-creased,while the levels of NLRP3,caspase-1,and GSDMD protein and LDH concentrations increased(all P＜0.05).There was no sig-nificant difference in other indexes(all P＞0.05).Conclusions Dex can improve propofol-induced learning memory impairment in developing rats,which may be related to the activation of PKA to down-regulate the NLRP3/caspase-1 signaling pathway,in order to re-lieving hippocampal pyroptosis.
DexmedetomidineDevelopmental phaseLearning and memory functionPropofolProtein kinase ARat
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