机构地区:[1]河南中医药大学,郑州450046 [2]呼吸疾病中医药防治省部共建协同创新中心,郑州450046
出 处:《中药药理与临床》2020年第5期100-104,共5页Pharmacology and Clinics of Chinese Materia Medica
基 金:国家重点研发计划:中医药现代化研究重点专项(2019YFC1708802);河南中医药大学2018年度博士科研基金(BSJJ2018-04)。
摘 要:目的:研究皂角刺水煎提取物对皮质酮(CORT)所致小鼠抑郁样行为的影响及其机制。方法:除正常组对照外,对C57BL/6小鼠皮下注射CORT,模型复制成功后,随机分为正常对照组、模型对照组、氟西汀5 mg/kg阳性组、皂角刺水提物1.67、3.33、6.67 g/kg组。糖水偏好(SPT)、悬尾实验(TST)、旷场实验(OFT)检测抑郁行为学指标,ELISA法测定血清神经递质水平,Western blot检测海马环磷酸腺苷(cAMP)、环磷腺苷效应元件结合蛋白(CREB)、脑源性神经营养因子(BDNF)蛋白的表达。结果:与正常对照组比较,模型对照组小鼠糖水偏好率和旷场实验行进距离显著降低(P<0.01),悬尾实验不动时间和血清CORT含量显著增加(P<0.01),神经递质5-羟色胺(5-HT)、多巴胺(DA)、去甲肾上腺素(NE)的含量显著降低,p-CREB/CREB、cAMP、BDNF的蛋白表达水平均显著下调(P<0.01)。与模型对照组比较,皂角刺水提物3个剂量组明显升高小鼠糖水偏好率(P<0.01),1.67、6.67 g/kg减少悬尾不动时间,1.67 g/kg增加旷场实验中的行进距离(P<0.05或P<0.01)。3.33、6.67 g/kg降低小鼠血清CORT含量(P<0.05或P<0.01),升高血清神经递质5-HT、DA、p-CREB/CREB含量,皂角刺水提物3个剂量组小鼠海马组织中cAMP、BDNF的蛋白表达水平明显上调(P<0.05或P<0.01)。结论:皂角刺水提物可能通过提高神经递质浓度和调节cAMP-CREB-BDNF通路来缓解皮质酮诱导的抑郁样行为。Objective:To study the effect and mechanism of water extract from Gleditsiae Spina on the depression-like behavior of mice induced by corticosterone(CORT).Methods:Except for the control group,C57BL/6 mice were subcutaneously injected with CORT.After the model was successfully established,the mice were randomly divided into the control group,the model control group,5 mg/kg fluoxetine(FLX)positive group,Gleditsiae Spina decoction extract groups(1.67 g/kg,3.33 g/kg,6.67 g/kg).Sucrose preference test(SPT),tail suspension test(TST),and open field test(OFT)were used to detect depression behavior,ELISA was used to determine the level of serum neurotransmitters,Western blot was used to detect the effects of cAMP,cAMP-response element binding protein(CREB),and brain-derived neurotrophic factor protein(BDNF)expression in hippocampus.Results:Compared with the control group,in the model group,the sucrose preference rate and the travel distance in the open field experiment were significantly reduced(P<0.01),the immobility time in the tail suspension test and serum CORT content were significantly increased(P<0.01),while the levels of serotonin(5-HT),dopamine(DA),norepinephrine(NE)and the protein expression levels of p-CREB/CREB,cAMP,and BDNF significantly decreased(P<0.01).Compared with the model group,all extracts from Gleditsiae Spina significantly increased the sucrose preference rate of mice(P<0.01),the 1.67 g/kg and 6.67 g/kg drugs reduced the time of suspension,and 1.67 g/kg drug reduced the distance in the open field experiment(P<0.05 or P<0.01).In 3.33 g/kg and 6.67 g/kg groups,the serum CORT contents of mice were decreased(P<0.05 or P<0.01),and the levels of serum neurotransmitters 5-HT,DA and p-CREB/CREB were increased.While the protein expressions of cAMP and BDNF of mouse hippocampus in all doses of extracts groups were increased(P<0.05 or P<0.01).Conclusion:The extract from Gleditsiae Spina can alleviate the corticosterone-induced depression-like behavior by increasing the neurotransmitters levels and regulating t
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