右美托咪定对老年大鼠麻醉后认知功能障碍的预防作用及机制研究OA

Objective:To explore the preventive effect of Dexmedetomidine on cognitive dysfunction in aged rats after anesthe-sia and its possible mechanism.Methods:A total of 48 rats were randomly divided into control group,model group,Dex group and Dex+alpha-bungarotoxin(α-BGT)group with 12 rats in each group.Establishment of anesthetic model with isoflurane.1.5 hours be-fore modeling,the Dex+α-BGT group received intraperitoneal injection of 1 μg/kg α-BGT;and 1 hour before modeling,both the Dex group and the Dex+α-BGT group were administered 4 μg/kg Dex through intraperitoneal injection.The cognitive function of rats was tested.The synaptic structure of the hippocampus was quantified using Golgi-Cox staining.The levels of inflammatory factors in brain tissue were detected by ELISA.qRT-PCR,immunofluorescence,and Western blot were used to detect the expressions of α7 nicotinic acetylcholine receptors(α7nAChR),high mobility group box 1 protein(HMGB1)/receptor for advanced glycation end products(RAGE)/nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)(HMGB1/RAGE/NF-κB)signaling pathway-related molecules in the brain tissue.Results:Compared with control group,RI value,percentage of travel distance and total distance in the first quadrant,the percentage of elapsed time and total time,dendrite length,synaptic density,the number of dendrite intersections with concentric circles,α7nAChR mRNA,and protein expression were decreased in the model group,Dex group and Dex+α-BGT group(P<0.05),with an extended escape latency(P<0.05).In contrast,TNF-α,IL-1β,IL-6,HMGB1 mRNA,protein,RAGE and p-NF-κB protein expressions were increased(P<0.05).Compared with the model group,the RI value,the percentage of travel distance and total distance in the first quadrant,the percentage of elapsed time and total time,dendrite length,synaptic density,the number of dendrite intersections with concentric circles,α7nAChR mRNA,and protein expression increased in the Dex group(P<0.05),with a shortened escape latency(P<0.05).In contrast,TNF-α,IL-1β,IL-6,HMGB1 mRNA,protein,RAGE,and p-NF-κB protein ex-pressions were decreased(P<0.05).Conclusion:Dex prevents post-anesthetic cognitive dysfunction in aged rats by inhibiting the HMGB1/RAGE/NF-κB signaling pathway via activating α7nAChR.