枣仁安神方对抑郁大鼠脑内单胺神经递质、HPA轴及CREB/BDNF信号通路的影响  

Effects of Zaoren Anshen Prescription on Monoamine Neurotransmitters, HPA Axis, and CREB/BDNF Signaling Pathway in the Brains of Depressed Rats

作　　者：李祥婷[1] 李婷婷[2] 项忆瑾 蔡敏[1] 向军[1] 张雯[1] LI Xiangting;LI Tingting;XIANG Yijin;CAI Min;XIANG Jun;ZHANG Wen(Zhongshan Hospital,Fudan University,Shanghai 200032,China;Shuguang Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]复旦大学附属中山医院,上海200032 [2]上海中医药大学附属曙光医院,上海201203

出　　处：《中医药信息》2024年第11期1-8,共8页Information on Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81903970);复旦大学附属中山医院优秀青年计划项目(2021ZS YQ21)。

摘　　要：目的:研究枣仁安神方(Zaoren Anshen Prescription,ZAP)对慢性不可预知温和应激(chronic mild unpredictable stress,CUMS)抑郁模型大鼠脑内单胺类神经递质、HPA轴功能及CREB/BDNF信号通路的影响,探讨其抗抑郁作用机制。方法:成年雄性SD大鼠随机分为正常对照组10只和模型组30只;正常对照组(CUMS-/Vehicle组)不给予任何处理,模型组给予孤养联合慢性不可预知温和应激,4周后再根据糖水偏好实验基线值评分将模型组大鼠分为3个亚组,分别为抑郁模型组(CUMS+/Vehicle组)、氟西汀阳性对照组(CUMS+/FLU组)和枣仁安神方治疗组(CUMS+/ZAP组)。各组均在造模时灌胃给药,给药时间为4周,CUMS-/Vehicle组大鼠给予0.9%生理盐水10 mL/(kg·d),CUMS+/ZAP组给予枣仁安神方15 g/(kg·d),CUMS+/FLU组给予FLU 10 mg/(kg·d)。实验结束后进行旷场实验、糖水偏好实验、强迫游泳实验和新环境进食抑制实验观察。应用高效液相色谱法检测大鼠海马组织单胺类神经递质及其代谢产物的浓度;采用酶联免疫吸附测定法检测各组大鼠血清促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)、皮质酮(corticosterone,CORT)含量;采用Western blot检测大鼠海马组织中p-CREB、BDNF蛋白表达含量。结果:造模8周(ZAP治疗4周)后,与CUMS-/Vehicle组相比,CUMS+/Vehicle组大鼠体质量增量明显降低(P<0.01),糖水偏好显著降低(P<0.01),中心区域停留时间以及中心区域停留次数均减少(P<0.01),强迫游泳中不动时间显著增加(P<0.01),在新环境下的摄食潜伏期显著延长(P<0.01),血清ACTH、CORT的含量明显升高(P<0.01),海马组织单胺类神经递质水平显著降低(P<0.01),海马组织BDNF、p-CREB蛋白表达降低(P<0.01)。在应激持续存在的情况下,给予枣仁安神方治疗,上述异常的指标均得到明显改善,差异均有统计学意义(P<0.05,P<0.01)。结论:枣仁安神方可有效改善抑郁模型大鼠的行为学指标,可通过提高海马单胺类�Objective:To investigate the effects of Zaoren Anshen Prescription(ZAP)on monoamine neurotransmitters,HPA axis function,and the CREB/BDNF signaling pathway in the brains of rats with chronic mild unpredictable stress(CUMS)-induced depression,and to preliminarily explore its antidepressant mechanism.Methods:Adult male Sprague-Dawley(SD)rats were randomly divided into a normal control group(CUMS-/Vehicle,n=10)and a model group(CUMS+/Vehicle,n=30).The normal control group received no treatment,while the model group underwent solitary housing combined with chronic mild unpredictable stress for 4 weeks.Afterward,based on baseline scores from a sucrose preference test,the model group was subdivided into three groups:the depression model group(CUMS+/Vehicle),the fluoxetine positive control group(CUMS+/FLU),and the Zaoren Anshen Prescription treatment group(CUMS+/ZAP).All groups received intragastric administration for 4 weeks,with the CUMS-/Vehicle group receiving saline(10 mL/kg·d),the CUMS+/ZAP group receiving ZAP(15 g/kg·d),and the CUMS+/FLU group receiving fluoxetine(10 mg/kg·d).Behavioral tests including the open field test,sucrose preference test,forced swimming test,and novelty-suppressed feeding test were conducted after treatment.High-performance liquid chromatography(HPLC)was used to measure the concentrations of monoamine neurotransmitters and their metabolites in the hippocampus.Enzyme-linked immunosorbent assay(ELISA)was used to determine serum levels of adrenocorticotropic hormone(ACTH)and corticosterone(CORT).Western blot was employed to detect the expression levels of p-CREB and BDNF proteins in the hippocampus.Results:After 8 weeks of modeling(4 weeks of ZAP treatment),compared to the CUMS-/Vehicle group,the CUMS+/Vehicle group showed significant decreases in body weight gain(P<0.01),sucrose preference(P<0.01),time and frequency of staying in the central area(P<0.01),and significant increases in immobility time during forced swimming(P<0.01)and feeding latency in a novel environment(P<0.01).Serum ACT

关 键 词：枣仁安神方 慢性不可预见性温和应激 抑郁症 神经递质 HPA轴 CREB/BDNF通路 

分 类 号：R285.5[医药卫生—中药学]