比较不同剂量皮质酮注射致小鼠抑郁行为变化  

Dose-related changes in depressive behavior in mice induced by corticosterone injection

作　　者：阿如罕 李俊[2] 龚琴 何明珍[1,2] 何北兰[1] 邹恩国 冯育林 A Ruhan;LI Jun;GONG Qin;HE Mingzhen;HE Beilan;ZOU Enguo;FENG Yulin(Jiangxi University of Chinese Medicine,Nanchang 330006,China;National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine,Nanchang 330006)

机构地区：[1]江西中医药大学,南昌330006 [2]中药固体制剂制造技术国家工程研究中心,南昌330006

出　　处：《中国比较医学杂志》2025年第2期85-93,共9页Chinese Journal of Comparative Medicine

基　　金：江西中医药大学科技创新团队支持计划项目(CXTD22001)。

摘　　要：目的观察不同剂量皮质酮(corticosterone,CORT)诱导的小鼠抑郁行为和神经元损伤的变化,摸索CORT致小鼠抑郁模型的最佳剂量。方法将40只雄性C57BL/6J小鼠随机分成4组:对照组、CORT(20、40和60 mg/kg)组,相应药物干预连续4周。经糖水偏好性实验、强迫游泳实验、悬尾实验和旷场实验检测CORT皮下注射4周对小鼠行为学的改变;苏木精-伊红(HE)染色和尼氏染色观察小鼠海马CA1区和前脑皮层区神经元形态的变化;酶联免疫吸附测定(ELISA)检测血清中5-羟色胺(5-hydroxytryptamine,5-HT)的含量;比较不同剂量的CORT致小鼠抑郁样行为学变化。结果与对照组相比,CORT(20、40和60 mg/kg)组小鼠体重均下降(P<0.05)、蔗糖溶液的偏好降低(P<0.01);CORT 20 mg/kg、40 mg/kg组强迫游泳实验小鼠不动时间延长(P<0.01);悬尾实验中CORT 40 mg/kg组小鼠不动时间延长(P<0.05);CORT 40 mg/kg和60 mg/kg组旷场实验小鼠总路程、进入中心区域次数降低和小鼠边缘区域停留时间延长(P<0.05),小鼠CORT 40 mg/kg组旷场平均速度明显降低(P<0.05)。此外,CORT注射导致不同程度小鼠海马CA1区和前脑皮层区神经元细胞形态不完整、细胞变形、细胞核固缩的现象。CORT 40 mg/kg和60 mg/kg组血清中5-HT水平降低(P<0.05)。结论CORT(20、40和60 mg/kg)组均可诱导小鼠产生不同程度的抑郁样行为学改变和神经元损伤,其中CORT 40 mg/kg组影响较明显。本实验条件下,初步认为40 mg/kg是复制CORT所致小鼠抑郁模型的最佳剂量。Objective To observe the depressive behavior and neuronal damage induced by different doses of corticosterone(CORT)in mice,and to explore the optimal dose for a corticosterone-induced depression model in mice.MethodsForty male C57BL/6J mice were divided randomly into four groups:control group and low,medium,and high CORT groups(20,40,and 60 mg/kg,respectively),treated with the corresponding drug dose by subcutaneous injection for 4 weeks.Behavioral changes in mice after corticosterone administration for 3 and 4 weeks were detected by sugar water preference,forced swimming,tail suspension,and open field tests.Morphological changes in neurons in the hippocampal CA1 area and forebrain cortex area were observed by hematoxylin-eosin(HE)and Nissl staining.Serum levels of 5-hydroxytryptamine(5-HT)were detected by enzyme-linked immunosorbent assay.Depression-related behavioral changes induced by different doses of corticosterone were compared.Results The bodyweights of mice in all three CORT groups(20,40,and 60 mg/kg)decreased(P<0.05)and the preference for sucrose solution decreased(P<0.01)compared with the findings in the control group.The immobility time in the forced swimming test was prolonged in the CORT 20 and 40 mg/kg groups(P<0.01)and the immobility time of mice in the tail suspension test was prolonged in the CORT 40 mg/kg group(P<0.05).The total distance,the length of time spent in the peripheral area was prolonged and the time entering the central area in the open-field experiment were decreased in the CORT 40 and 60 mg/kg groups(P<0.05),and average speed were decreased in the CORT 40 mg/kg group(P<0.05).In addition,CORT injection result ed in abnormal neuronal cell morphology,cell deformation,and nuclear condensation in the hippocampal CA1 and forebrain cortex areas,to different degrees.Serum 5-hydroxytryptamine levels were reduced in the CORT 40 and 60 mg/kg groups(P<0.05).Conclusions CORT 20,40,and 60 mg/kg can induce depression-like behavioral changes and neuronal damage in mice to varying degrees,with the

关 键 词：皮质酮 抑郁 苏木精-伊红染色 神经元损伤 5-羟色胺 

分 类 号：R-33[医药卫生]