桂附汤对慢性不可预见性温和应激小鼠抑郁样行为及海马脑源性神经营养因子表达的影响

Effects of Guifu decoction on depression-like behavior and hippocampal brain-derived neurotrophic factor expression in chronic unpredictive mild stress mice

目的研究桂附汤对慢性不可预见性温和应激(chronic unpredictive mild stress,CUMS)小鼠抑郁样行为的干预作用及对脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)表达的影响。方法利用CUMS法诱导C57BL/6小鼠构建抑郁模型,通过蔗糖偏好实验、旷场实验、悬尾实验观察桂附汤对小鼠抑郁样行为的影响,采用实时荧光定量-聚合酶链式反应(real-time fluorescence quantitative-polymerase chain reaction,RTFQ-PCR)检测小鼠海马组织BDNF mRNA表达,免疫组化法(immunohistochemistry,IHC)检测小鼠海马区BDNF蛋白定位表达,苏木素-伊红(hematoxylin and eosin,HE)染色观察海马组织形态学的变化。结果与对照组相比,模型组体质量下降(P<0.01),肾上腺指数升高(P<0.05),糖水偏好度显著降低(P<0.01),旷场实验总静止时间显著升高(P<0.01)、进入中央区域次数显著降低(P<0.01),悬尾实验静止时间显著升高(P<0.01),BDNF蛋白表达和m RNA水平显著降低(P<0.01);与模型组相比,桂附汤高剂量组(P<0.01)、中剂量组和氟西汀组(P<0.05)肾上腺指数显著降低,桂附汤中、高剂量组和氟西汀组旷场实验总静止时间显著降低(P<0.01)、进入中央区域的次数显著增加(P<0.01),各干预组小鼠糖水偏好度显著增加(P<0.05),旷场实验总静止时间显著降低(P<0.01)、进入中央区域的次数显著增加(P<0.01),悬尾实验静止时间显著降低(P<0.01),海马BDNF m RNA及蛋白表达都显著增加(P<0.01),海马组织病理损伤明显改善。结论桂附汤可改善CUMS诱导的小鼠抑郁样行为,上调BDNF表达,保护海马神经元的结构和功能。

Objective To study the effects of Guifu decoction on depression-like behavior and the expression of brain-derived neurotrophic factor(BDNF)in a chronic unpredictive mild stress(CUMS)mice model.Methods CUMS method was used to induce depression model in C57BL/6 mice.Sucrose preference test,open-field test and tail suspension test were used to observe the effect of Guifu decoction on depression-like behavior of mice.Real-time fluorescence quantitative-polymerase chain reaction(RTFQ-PCR)was used to detect the expression of BDNF mRNA in hippocampus of mice.Immunohistochemistry(IHC)was used to detect the localized expression of BDNF protein in the hippocampus of mice,and hematoxylin and eosin(HE)staining was used to observe the histomorphological changes of hippocampus.Results Compared with the control group,the body weight of mice in each intervention group was significantly decreased(P<0.01).In model group,adrenal index(AI)was significantly increased(P<0.05),sugar preference ratio was significantly decreased(P<0.01),total immobility time of open-field test was significantly increased(P<0.01),entries into the central zone was significantly decreased(P<0.01),the immobility time of tail suspension test was significantly increased(P<0.01),and BDNF protein expression and mRNA levels in hippocampus were significantly decreased in the model group(P<0.01).Compared with the model group,the AI of Guifu decoction high-dose group(P<0.01),medium-dose group and fluoxetine group(P<0.05)were significantly decreased,and the sugar preference ratio of mice in each intervention group was significantly increased(P<0.05).The total immobility time of open field test was significantly decreased(P<0.01),the entries into the central zone was significantly increased(P<0.01)in Guifu decoction high-dose group,medium-dose group and fluoxetine group.The sugar preference ratio was significantly increased(P<0.05),the immobility time of tail suspension test was significantly decreased(P<0.01),the relative expression levels of BDNF mRNA and protein in hippocampus were significantly increased(P<0.01),and the pathological damage of hippocampus was significantly improved in each intervention groups.Conclusion Guifu decoction can improve the depression-like behavior induced by CUMS,up-regulate BDNF expression,and protect the structure and function of hippocampal neurons.