林下参提取物对慢性不可预知温和应激模型小鼠抑郁样行为及HPA轴影响

王伟; 章国磊; 李铮; 陆勃帆; 李慧; 吴巍

doi:10.13386/j.issn1002-0306.2022090267

林下参提取物对慢性不可预知温和应激模型小鼠抑郁样行为及HPA轴影响

Effects of Understory Panax ginseng Extract on Depression-like Behavior and HPA Axis of Chronic Unpredictable Mild Stress Model Mice

摘要

摘要: 目的：研究林下参提取物（understory Panax ginseng extract，UPGE）对慢性不可预知温和刺激（chronic unpredictable mild stress，CUMS）模型小鼠抑郁样行为及下丘脑-垂体-肾上腺（hypothalamic-pituitary-adrenal，HPA）轴的影响。方法：超高效液相色谱-串联质谱（UPLC-MS/MS）方法鉴别UPGE中的皂苷成分。将60只雄性昆明小鼠随机分为空白组（Control），模型组（CUMS），文拉法辛组（10 mg·kg⁻¹ Ven）以及林下参提取物组（100 mg·kg⁻¹ UPGE）。除空白组外，均采用CUMS诱导各组小鼠抑郁，灌胃给药21 d后通过小鼠体质量，进行糖水偏好实验，旷场实验，水迷宫实验分析其行为学变化；采用酶联免疫吸附测定法（enzyme linked immunosorbent assay，ELISA）检测促肾上腺皮质激素释放激素（corticotropin-releasing hormone，CRH），促肾上腺皮质激素（adrenocorticotropic hormone，ACTH）和皮质酮（corticosterone，CORT）的含量，苏木精-伊红染色（hematoxylin-eosin staining，HE）法观察小鼠海马CA1，CA3区神经元细胞病理变化，原位末端标记法（TUNEL）显色法检测海马区细胞凋亡情况。结果：UPGE中含16种皂苷成分。相比于模型组，UPGE给药组小鼠糖水偏好度显著提升（P<0.01）、旷场实验中水平运动距离增加和垂直站立次数增加（P<0.05，P<0.01）、水迷宫实验中逃避潜伏期降低（P<0.05）、增加目标象限停留时间、穿越平台次数（P<0.05，P<0.01）、能够缓解海马神经元细胞的损伤，血浆中ACTH 、CORT 和CRH水平降低（P<0.05），海马区细胞凋亡率降低（P<0.05，P<0.01）。结论：UPGE有显著的抗抑郁作用，其作用机制可能与调节HPA轴功能有关。

Abstract: Objective: To explore the effect of understory Panax ginseng extract (UGPE) on depression-like behavior and hypothalamic-pituitary-adrenal (HPA) axis of chronic unpredictable mild stress (CUMS) model mice. Methods: Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) were used to detect the contents of ginsenosides. Totally 60 male Kunming mice were randomly divided into four groups: Control, model, positive venlafaxine (10 mg·kg⁻¹ Ven) and UGPE group (100 mg·kg⁻¹ UPGE). The depression model was induced by CUMS in mice except for those in the control group, they were received corresponding drug by intragastric administration for 21 days. The sucrose preference test, open field test and Morris water maze experiments were conducted to analyze their behavioral changes. The contents of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in plasma were measured by enzyme linked immunosorbent assay (ELISA). Hematoxylin-Eosin (HE) staining was used to investigate the pathological changes of neurons in the CA1 and CA3 area of hippocampus. The apoptosis of hippocampal neurons was observed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) method. Results: UPGE contained 16 ginsenosides. Compared with the model group, the UPGE group significantly improved sugar-water preference (P<0.01), increased horizontal movement distance, and increased vertical standing times in the absenteeism experiment (P<0.05, P<0.01). Shortened the escape latency in Morris water maze test (P<0.05). Increased the target quadrant residence time and the platform crossing times in Morris water maze test (P<0.05, P<0.01). UPGE would alleviate hippocampal neuron injury. The levels of ACTH, CORT and CRH in plasma were decreased (P<0.05), the apoptosis of hippocampal cells was decreased (P<0.05, P<0.01). Conclusion: The UGPE would improve antidepressant behavior of CUMS mice, and its mechanism might be related to the regulation of HPA axis function.