江西中医药大学
江西中医药大学科技创新团队支持计划项目(CXTD22001) 。
Jiangxi University of Chinese Medicine
Jiangxi University of Chinese Medicine Science and Technology Innovation team supports project(CXTD22001) 。
【摘要】 目的 观察不同剂量皮质酮（CORT）诱导的小鼠抑郁行为和神经元损伤的变化，摸索皮质酮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：正常对照组，皮质酮组（低、中、高，20、40、60 mg/kg ），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，检测皮质酮皮下注射3周和4周对小鼠行为学的改变；苏木精-伊红染色（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-HT）的含量；比较不同剂量的皮质酮致小鼠抑郁样行为学变化。结果 与对照组相比，皮质酮剂量组（20、40、60 mg/kg ）小鼠体重均下降（P＜0.05）、蔗糖溶液的偏好降低（P＜0.01）；皮质酮20、40 mg/kg组强迫游泳实验小鼠不动时间延长（P＜0.01）；皮质酮40 mg/kg组悬尾实验小鼠不动时间延长（P＜0.05）；皮质酮40、60 mg/kg组旷场实验小鼠总路程、平均速度和进入中心区域次数降低（P＜0.05），小鼠边缘区域停留时间延长（P＜0.05）。此外，皮质酮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。皮质酮40 、60 mg/kg组血清中5-HT水平降低（P＜0.05）。结论 皮质酮20、40、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40 mg/kg皮质酮组影响较明显。本实验条件下，初步认为40 mg/kg是复制皮质酮所致小鼠抑郁模型的最佳剂量。
【Abstract】Objective To observe the changes of depressive behavior and neuronal damage induced by different doses of corticosterone (CORT) in mice, and to explore the best dose of corticosterone-induced depression model in mice. Methods Forty male C57BL/6J mice were randomly divided into four groups: normal control group and corticosterone group (low, medium and high, 20, 40 and 60 mg/kg), and the corresponding drug intervention lasted for 4 weeks. The behavioral changes of mice after subcutaneous injection of corticosterone for 3 and 4 weeks were detected by sugar water preference test, forced swimming test, tail suspension test and open field test. Hematoxylin-eosin staining (HE) and Nissl staining were used to observe the morphological changes of neurons in hippocampal CA1 area and forebrain cortex area of mice. Enzyme-linked immunosorbent assay (ELISA) was used to detect the content of 5- hydroxytryptamine (5-HT) in serum. To compare the behavioral changes of depression in mice induced by different doses of corticosterone. Results Compared with the control group, the weight of mice in corticosterone dosage groups (20 mg/kg, 40 mg/kg and 60 mg/kg) decreased (P < 0.05) and the preference of sucrose solution decreased (P < 0.01). The immobility time of forced swimming mice in corticosterone 20 mg/kg and 40 mg/kg groups was prolonged (P < 0.01). The immobility time of mice in the 40 mg/kg corticosterone group was prolonged (P < 0.05). The total distance, the average speed and the times of entering the central area of the open-field experimental mice in the corticosterone 40 mg/kg and 60 mg/kg groups decreased (P < 0.05), and the stay time in the peripheral area of the mice was prolonged (P < 0.05). In addition, corticosterone injection resulted in incomplete neuronal cell morphology, cell deformation and nuclear condensation in hippocampal CA1 area and forebrain cortex area of mice in different degrees. The level of 5-HT in serum of 40 mg/kg and 60 mg/kg corticosterone decreased (P < 0.05). Conclusion Corticosterone at 20 mg/kg, 40 mg/kg and 60 mg/kg can induce depression-like behavioral changes and neuronal damage in mice to varying degrees, and the effect of corticosterone at 40 mg/kg is more obvious. Under the experimental conditions, it is preliminarily considered that 40 mg/kg is the best dose to replicate the depression model induced by corticosterone in mice.
