中国中西医结合杂志2025，Vol.45Issue(10)：1230-1239,10.DOI:10.7661/j.cjim.20250813.149
龟鹿二仙胶调控海马CA1区小清蛋白促进创伤后应激障碍大鼠恐惧记忆消退
Guilu Erxian Glue Promotes Fear Memory Extinction in Post-traumatic Stress Disorder Rats by Modulation of Parvalbumin in Hippocampal CA1 Region
摘要
Abstract
Objective To investigate the intervention effect and mechanism of Guilu Erxian Glue(GEG)on fear memory extinction in a rat model of post-traumatic stress disorder(PTSD).Methods SD rats were randomly divided into control group,model group,GEG group(3.6 g/kg),and paroxetine group(10 mg/kg),with 10 rats in each group.A 6-day continuous inescapable foot shock was used as the stressor to establish a PTSD rat model.From the 1st day,the intervention group was given the corresponding drug by gavage for 21 consecutive days.The elevated plus maze test and contextual fear conditioning test were employed to assess the anxiety levels and fear behaviors of the rats.Western Blot was used to detect the expression of parvalbumin(PV),aggrecan(ACAN),and brevican(BCAN)in the hippocampus of rats in each group.Immunofluorescence techniques were applied to observe the expression of cellular oncogen fos(c-fos),PV,perineuronal nets(PNN),postsynaptic density protein 95(PSD95),and the postsynaptic marker gephyrin in the hippocampal CA1 region of rats in each group.ELISA was used to measure the levels of matrix metalloproteinase(MMP)-2 and MMP-9 in the hippocampus of rats in each group.Results Compared with the control group,the total distance,percentage of open arm distance,percentage of open arm stay time,and percentage of open arm entry times decreased,the expression of PV protein in the hippocampus,the number of PV positive cells in the CA1 area,the number of PV positive cells without PNN encapsulation(PNN-PV),the number of PSD95 positive cells,and the content of MMP-2 all decreased in the model group(P＜0.05).The percentage of extracted test rigidity time,the percentage of generalized test rigidity time,the rigidity time in the extinction retention test,the rigidity time in block 1,2,and 3 of scene fear memory extinction training increased,and the expression of ACAN and BCAN proteins in the hippocampus,the proportion of PNN+PV positive cells among PV positive cells,and the number of PNN+PV positive cells increased in the model group(P＜0.05).Compared with the model group,the above-mentioned indicators had improved to varying degrees in GEG group(P＜0.05).The correlation analysis revealed that the percentage of the duration of rigidity in the scene fear extinction retention test was negatively correlated with the number of PV/c-fos double-positive cells in the CA1 region of the hippocampus(r=-0.3537,P＜0.05).Conclusions GEG may alleviate anxiety-like behavior,suppress fear memory generalization,and promote contextual fear memory extinction in PTSD rats.These effects are potentially mediated by enhancing the activation of PV intemeurons in the hippocampal CA1 region,modulating PV-PNN dysregulation,and regulating synaptic plasticity.关键词
龟鹿二仙胶/创伤后应激障碍/恐惧记忆/小清蛋白/神经元周围网络/突触可塑性Key words
Guilu Erxian Glue/post-traumatic stress disorder/fear memory/parvalbumin/perineuronal network/synaptic plasticity引用本文复制引用
王淑婷,张天鸽,吴丽丽,严灿,周海圣,范志欣,龚夏雨,李兰心,许汉芳,古敬娜,严玉琪,樊丽荟..龟鹿二仙胶调控海马CA1区小清蛋白促进创伤后应激障碍大鼠恐惧记忆消退[J].中国中西医结合杂志,2025,45(10):1230-1239,10.基金项目
国家自然科学基金资助项目(No.82074309) （No.82074309）
广东省基础与应用基础研究基金联合基金(No.2023A1515110172) （No.2023A1515110172）
中国博士后科学基金面上项目(No.2023M740864) （No.2023M740864）
