摘要
【目的】研究β-HgS对抗抑郁药物缓解小鼠抑郁的增效作用.【方法】将小鼠随机分为空白对照组、模型对照组、丙咪嗪组、β-HgS组、β-HgS+丙咪嗪组.空白组和模型组灌胃给予同样体积的淀粉混悬液,丙咪嗪组、β-HgS组和β-HgS+丙咪嗪组分别灌胃给予丙咪嗪(15 mg/kg)、β-HgS(338 mg/kg)和丙咪嗪(15 mg/kg)及β-HgS(338 mg/kg).在给药的同时,除空白对照组外,其他各组小鼠进行慢性束缚应激.连续灌胃给药21 d后,通过行为学试验、海马组织切片观察,测定大脑皮层5-羟色胺(5-HT)、去甲肾上腺素(NE)含量、海马脑源性神经营养因子(BDNF)含量和促肾上腺皮质激素释放激素(CRH)含量,评价药物的抗抑郁作用.【结果】与模型组比较,β-HgS+丙咪嗪组小鼠抑郁行为程度显著降低,海马组织损伤程度显著减轻,皮层5-HT、NE以及海马BDNF含量显著升高,海马CRH含量显著降低(P<0.05或P<0.001).与丙咪嗪组比较,β-HgS+丙咪嗪组小鼠悬尾试验和强迫游泳试验的不动时间更少(P<0.05),海马DG区结构损伤更小,皮层NE和海马BDNF含量更高(P<0.05).【结论】β-HgS对丙咪嗪缓解小鼠抑郁具有增效作用,其增效作用可能是通过单胺类神经递质和神经营养因子途径来实现的.
【Objective】To investigate the synergistic effect ofβ-HgS on anti-depression activity of imipramine in chronic restraint stress-stimulated mice.【Method】Male KM mice were randomly divided into 5 groups(n=8):normal,model,IMI,β-HgS,IMI+β-HgS.Mice in normal and model groups were intragastrically administrated 2%((w/v))starch solution.β-HgS,IMI and SER were respectively dissolved in 2%(w/v)starch solution,and then intragastrically administrated to the mice in drug treated groups(β-HgS,IMI,and IMI+β-HgS groups)as the dosages of 338 mg/kg(β-HgS)and 15 mg/kg(IMI)per day for 3 weeks.Meantime,the mice exposed to chronic restraint stress(CRS)per day for 3 weeks,except for the normal group.The anti-depression effect of drugs was evaluated using behavioral tests,hippocampus section observation,and the contents of serotonin(5-HT)and norepinephrine(NE)in the cerebral cortex,brain-derived neurotrophic factor(BDNF)in the hippocampus,and corticotropin-releasing hormone(CRH)assays.【Result】Compared with the model group,mice in IMI+β-HgS groups showed significantly lower degree of depression behaviors and hippocampal structural damage,their contents of cortical 5-HT and NE and hippocampal BDNF were significantly increased,but the content of hippocampal CRH were significantly decreased(P<0.05 or P<0.001).Compared with the IMI group,the immobility time in tail suspension test and forced swimming test was much lesser(P<0.05),the damage of hippocampal DG region was significantly weaker,the contents of cortical NE and hippocampal BDNF were significantly higher(P<0.05)in IMI+β-HgS group.【Conclusion】β-HgS has a synergistic effect on promoting anti-depression activity of imipramine in CRS stimulated mic,and its synergistic effect may be via monoamine neurotransmitter and neurotrophic factor pathways.
作者
乔亚俊
高婷婷
李岑
张明
魏立新
毕宏涛
QIAO Ya-jun;GAO Ting-ting;LI Cen;ZHANG Ming;WEI Li-xin;BI Hong-tao(Northwest Institute of Plateau Biology,Chinese Academy of Science,CAS Key Laboratory of Tibetan Medicine Research and Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation,Xining 810001,China;Department of Psychology,School of Public Health,Southern Medical University,Guangzhou 510515,China;University of Chinese Academy of Sciences,Beijing 100049,China)
出处
《甘肃农业大学学报》
CAS
CSCD
北大核心
2020年第6期10-18,共9页
Journal of Gansu Agricultural University
基金
国家重点研发计划项目(2018YFC1708006)
中国博士后科学基金项目(2019M652982)
青海省重点实验室发展建设专项(2017-ZJ-Y08)。
关键词
β-HgS
丙咪嗪
抑郁
慢性束缚应激
联合用药
β-HgS
imipramine
depression
chronic restraint stress model
combination drug
