过刊浏览

不同诱导方式下小鼠抑郁模型的比较研究

李佩佩^1,2, 王硕¹, 陈涛¹, 龙若兰^1,2, 冯丹^1,2, 卫阳飞^1,2, 宋志博^1,2, 李玉林¹, 孙菁^1,*

¹青海省青藏高原特色生物资源研究重点实验室，中国科学院西北高原生物研究所，西宁 810008；²中国科学院大学，北京 100049

摘要

本文旨在比较不同抑郁模型诱导方式的效果。将昆明小鼠随机分为慢性温和不可预知性应激(chronic unpredictable mild stress, CUMS)组、皮质酮(corticosterone, CORT)组及CUMS+CORT组(CC组)。CUMS组接受CUMS刺激4周，CORT组每天腹股沟皮下注射20 mg/kg CORT，共给药3周；CC组同时接受CUMS刺激和CORT给药。各组分别设立正常组做对照。建模结束后，用强迫游泳试验(forced swimming test, FST)、悬尾试验(tail suspension test, TST)和糖水偏好试验(sucrose preference test, SPT)检测小鼠行为学变化，用ELISA试剂盒检测小鼠血清脑源性神经营养因子(brain-derived neurotrophic factor, BDNF)、5-羟色胺(5-hydroxytryptamine, 5-HT)和CORT水平，同时采集和分析小鼠血清衰减全反射(attenuated total refraction, ATR)谱图，最后用HE染色法检测小鼠脑组织形态变化。结果显示，CUMS及CC组小鼠的体重显著降低。三组小鼠在FST和TST中不动时间没有显著变化，而CUMS及CC组小鼠糖水偏好显著降低(P < 0.05)。CORT及CC组小鼠血清5-HT水平显著降低，CUMS、CORT及CC组小鼠血清BDNF和CORT水平无显著变化。和各自的正常组相比，三组小鼠血清ATR一维谱图没有显著差异；谱图一阶导数的差谱分析结果显示，CORT组与自身正常组差异最大，其次是CUMS处理组。三组小鼠海马区结构均遭到了破坏。以上结果提示，CORT和CC处理均能成功构建抑郁模型，CORT模型效果优于CC模型，因此可利用CORT诱导进行昆明小鼠抑郁模型的建立。

关键词： 小鼠抑郁模型; 慢性温和不可预知性应激; 皮质酮

Comparison of mouse models of depression induced by different modeling methods

LI Pei-Pei^1,2, WANG Shuo¹, CHEN Tao¹, LONG Ruo-Lan^1,2, FENG Dan^1,2, WEI Yang-Fei^1,2, SONG Zhi-Bo^1,2, LI Yu-Lin¹, SUN Jing^1,*

¹Qinghai Key Laboratory of Qinghai-Tibet Plateau Biological Resource, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, China；²University of Chinese Academy of Sciences, Beijing 100049, China

Abstract

The present article was aimed to compare the effectiveness of different induction methods for depression models. Kunming mice were randomly divided into chronic unpredictable mild stress (CUMS) group, corticosterone (CORT) group, and CUMS+CORT (CC) group. The CUMS group received CUMS stimulation for 4 weeks, and the CORT group received subcutaneous injection of 20 mg/kg CORT into the groin every day for 3 weeks. The CC group received both CUMS stimulation and CORT administration. Each group was assigned a control group. After modeling, forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT) were used to detect the behavioral changes of mice, and the serum levels of brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT) and CORT were detected with ELISA kits. Attenuated total refraction (ATR) spectra of mouse serum were collected and analyzed. HE staining was used to detect morphological changes in mouse brain tissue. The results showed that the weight of model mice from the CUMS and CC groups decreased significantly. There was no significant change in immobility time of model mice from the three groups in FST and TST, while the glucose preference of model mice from the CUMS and CC groups was significantly reduced (P < 0.05). The serum 5-HT levels of model mice from the CORT and CC groups were significantly reduced, while the serum BDNF and CORT levels of model mice from the CUMS, CORT, and CC groups showed no significant changes. Compared with their respective control groups, the three groups showed no significant difference in the one-dimensional spectrum of serum ATR. The difference spectrum analysis results of the first derivative of the spectrogram showed that the CORT group had the greatest difference from its respective control group, followed by the CUMS group. The structures of hippocampus in the model mice from the three groups were all destroyed. These results suggest that both CORT and CC treatments can successfully construct a depression model, and the CORT model is more effective than the CC model. Therefore, CORT induction can be used to establish a depression model in Kunming mice.

Key words: depression model; chronic unpredictable mild stress; corticosterone

收稿日期：　　录用日期：

通讯作者：孙菁　　E-mail: sunj@nwipb.cas.cn

引用本文：

李佩佩, 王硕, 陈涛, 龙若兰, 冯丹, 卫阳飞, 宋志博, 李玉林, 孙菁. 不同诱导方式下小鼠抑郁模型的比较研究[J]. 生理学报 2023; 75 (3): 379-389.

LI Pei-Pei, WANG Shuo, CHEN Tao, LONG Ruo-Lan, FENG Dan, WEI Yang-Fei, SONG Zhi-Bo, LI Yu-Lin, SUN Jing. Comparison of mouse models of depression induced by different modeling methods. Acta Physiol Sin 2023; 75 (3): 379-389 (in Chinese with English abstract).