摘要
目的 初步探讨绝经后脂质代谢紊乱是否参与抑郁症状的形成。方法 24只LDLR-/-和16只WT C57BL/6J雌鼠,分为5组(n=8),分别为:WT+普通饮食组(WT)、WT+高脂饮食组(WT-H)、LDLR-/-去卵巢+普通饮食组(LDLR-/-)、LDLR-/-去卵巢+高脂饮食组(LDLR-/--H)、LDLR-/-去卵巢+高脂饮食+辛伐他汀组(XF),连续喂养3个月。LDLR-/-雌鼠双侧卵巢摘除联合高脂饮食建立绝经后脂质代谢紊乱模型。检测小鼠体重、脑总胆固醇(TC)及海马ERα、ERβ水平、抑郁行为、脑内5-HT水平;对脑TC水平和抑郁相关指标进行相关性分析。结果 (1)LDLR-/--H组可复制绝经后脂质代谢紊乱特征,表现为小鼠体重显著增加、脑TC水平显著升高、海马ERβ表达明显下降;(2)LDLR-/--H组小鼠水平和垂直运动均显著降低,TST静止时间显著增加,脑5-HT水平显著降低;(3)XF组小鼠脑TC水平显著下降、抑郁行为明显改善、5-HT水平明显提高;(4)小鼠脑TC水平与5-HT水平及抑郁样行为显著相关。结论 绝经后脂质代谢紊乱能诱导抑郁症状发生,通过调节脂质代谢可以显著改善抑郁症状。
Objective To investigate whether postmenopausal lipid metabolism disorder is involved in the development of depressive symptoms.Methods Twenty-four LDLR-/-and sixteen WT C57BL/6J female mice were divided into five groups(n=8):WT+normal diet group(WT),WT+high-fat diet group(WT-H),ovariectomized LDLR-/-+normal diet group(LDLR-/-),ovariectomized LDLR-/-+high-fat diet group(LDLR-/--H),and ovariectomized LDLR-/-+high-fat diet+simvastatin group(XF).Mice were fed continuously for 3 months.The postmenopausal lipid metabolism disorder model was established in LDLR-/-female mice after bilateral ovariectomy combined with a high-fat diet.Body weight,total cholesterol(TC),ERα,and ERβlevels in the hippocampus,depressive behavior,and 5-HT levels in the brain were determined.The correlation between the brain TC level and depression-related indexes was analyzed.Results(1)The LDLR-/--H group successfully replicated the characteristics of postmenopausal lipid metabolism disorder,which showed a significant increase in body weight,a notable increase in the brain TC level,and a significant decrease in expression of ERβin the hippocampus.(2)Horizontal and vertical locomotor activities of the LDLR-/--H group were significantly decreased,the immobilized time of TST was significantly increased,and the brain 5-HT level was significantly decreased.(3)The brain TC level of the XF group was significantly decreased,depressive behavior was significantly improved,and the 5-HT level was significantly increased.(4)Correlation analysis showed that the TC level in the brain was significantly correlated to the 5-HT level and depression-like behaviors.Conclusions Postmenopausal lipid metabolism disorder induces depressive symptoms,and depression symptoms can be significantly improved by regulating lipid metabolism disorder.
作者
沈皓天
姜俊杰
晁滢
洪敏
郑劼
卞慧敏
SHEN Haotian;JIANG Junjie;CHAO Ying;HONG Min;ZHENG Jie;BIAN Huimin(Department of Pharmacology,School of Medicine&Holistic Integrative Medicine,Nanjing University of Chinese Medicine,Nanjing 210023;China.2.Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica,School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023)
出处
《中国实验动物学报》
CAS
CSCD
北大核心
2023年第6期733-742,共10页
Acta Laboratorium Animalis Scientia Sinica
基金
国家自然科学基金(81774029,81703733,82274168)。
关键词
LDLR-/-小鼠
绝经后脂质代谢紊乱模型
抑郁症状
相关性分析
LDLR-/-mice
postmenopausal lipid metabolism disorder
depressive symptoms
correlation analysis Conflicts of Interest:The authors declare no conflict of interest.
