REV-ERB激动剂SR9009和LXH0225对过度训练所致小鼠情感障碍和认知损伤的改善作用  

Effects of SR9009 and LXH0225,REV-ERB agonists,on mood disor⁃ders and cognitive impairment in over-training mice

作　　者：邓琦 何新华 肖智勇 周文霞 DENG Qi;HE Xinhua;XIAO Zhiyong;ZHOU Wenxia(Nanjing University of Chinese Medicine,Nanjing 210023,China;State Key Laboratory of National Security Specially Needed Medicines,Academy of Military Medical Sciences,Beijing 100850,China)

机构地区：[1]南京中医药大学,江苏南京210023 [2]军事医学研究院国家安全特需药品全国重点实验室,北京100850

出　　处：《中国药理学与毒理学杂志》2024年第11期816-825,共10页Chinese Journal of Pharmacology and Toxicology

摘　　要：目的 研究生物钟分子核受体亚家族1组D成员(REV-ERB)激动剂SR9009和LXH0225对过度训练致情感障碍和认知损伤的影响。方法 将雄性C57BL/6J小鼠随机分为正常对照组、过度训练模型组、模型+氟西汀(15 mg·kg^(-1))组、模型+SR9009(100 mg·kg^(-1))组和模型+LXH0225(50 mg·kg^(-1))组。正常对照组小鼠不给任何应激,ip给予15%蓖麻油;模型组和模型+药物处理组小鼠持续18 d每天置19~21℃水中强迫游泳20 min(即应激处理),应激前30 min分别ip给予15%蓖麻油或相应药物。于给药后第15~18天,依次检测小鼠自主活动能力,采用转棒疲劳实验和负重游泳实验检测体能,采用旷场实验和爬梯实验检测焦虑样行为,采用悬尾实验和强迫游泳实验检测抑郁样行为,采用新物体识别实验和Y迷宫实验检测认知功能,采用ELISA检测血清皮质酮含量。结果 与正常对照组相比,模型组小鼠自主活动显著增加(P<0.01),出现爬梯实验爬梯次数和直立次数显著增加(P<0.01)的焦虑样行为、强迫游泳不动时间显著延长(P<0.01)的抑郁样行为和Y迷宫自发交替反应正确率下降(P<0.01)的认知损伤表现,血清皮质酮含量显著增加(P<0.01)。与模型组相比,模型+氟西汀组小鼠Y迷宫自发交替反应正确率显著增加(P<0.01),血清皮质酮含量显著降低(P<0.01);模型+SR9009组小鼠强迫游泳不动时间显著缩短(P<0.01),Y迷宫自发交替反应正确率显著增加(P<0.05),血清皮质酮含量显著减少(P<0.01);模型+LXH0225组小鼠转棒疲劳实验落棒潜伏期显著延长(P<0.05),强迫游泳不动时间显著缩短(P<0.01),血清皮质酮含量显著减少(P<0.01)。结论 REV-ERB激动剂SR9009和LXH0225可能对强迫游泳过度训练所致情感障碍和认知损伤具有改善作用。OBJECTIVE To study the effects of SR9009 and LXH0225,nuclear receptor subfamily 1 group D member(REV-ERB)agonists,on mood disorders and cognitive impairment in over-training mice.METHODS Male C57BL/6J mice were randomly divided into the normal control,over-training model,model+fluoxetine(15 mg∙kg^(-1)),model+SR9009(100 mg∙kg^(-1))and model+LXH0225(50 mg∙kg^(-1))groups.Mice in the normal control group were ip given15%cremophor without extra stress while those in other groups were ip given 15%cremophor or different drugs respectively 30 min before daily forced swimming stress.When stressed,mice were forced to swim in 19-21℃water for 20 min per day for 18 d.After that,locomotor activity was assessed.Rotarod test and weight-loaded swimming test were performed to measure physical strength,while open field test and stair-climbing test were performed to measure anxiety-like behavior.Tail suspension test and forced swimming test were used to measure depressionlike behavior while novel object recognition test and Y maze test were conducted to measure recogni⁃tion function.ELISA was used to measure serum corticosterone contents.RESULTS Compared with the normal control group,the locomotor activity of mice in the model group was significantly increased(P<0.01).There were anxiety-like behaviors with a significant increase in the number of times of stair-climb⁃ing and rearing(P<0.01).Depression-like behaviors were observed with a significant increase immobile time in forced swimming test(P<0.01).Cognitive impairment was manifested as decreased accuracy of Y-maze spontaneous alternation response(P<0.01).The corticosterone content was significantly elevated(P<0.01)in forced swimming mice.Compared with the model group,the accuracy of Y-maze spontaneous alternations was higher(P<0.01)and the content of serum corticosterone was lower(P<0.01)in the model+fluoxetine group.The immobile time was shorter(P<0.01),the spontaneous alternation response of Y maze was was less accurate(P<0.05)and serum corticosterone content was l

关 键 词：SR9009 LXH0225 强迫游泳 情感障碍 认知损伤 

分 类 号：R964[医药卫生—药理学]