阿魏酸钠对慢性不可预知温和刺激抑郁症大鼠抑郁行为的影响及其机制

目的：研究阿魏酸钠能否改善慢性不可预知温和刺激（chronic unpredicted mild stress，CUMS）抑郁大鼠的抑郁样行为并探讨其机制。方法：将SD大鼠随机分为正常对照组、CUMS模型组、CUMS+氟西汀（10 mg· kg^-1）组、CUMS+阿魏酸钠（50，100，150 mg· kg^-1）组。采用慢性温和不可预知应激方法建立大鼠抑郁模型，造模完成后，连续灌胃给药21 d。旷场实验、糖水偏爱实验、强迫游泳实验检测大鼠的行为学变化；生物化学方法检测大鼠海马超氧化物歧化酶（superoxide dismutase，SOD）和过氧化氢酶（catalase，CAT）活性及活性氧（reactive oxygen species，ROS）含量。实时荧光定量PCR（q-PCR）法检测海马炎症因子IL-1β、TNF-α、PGE₂及IL-10基因的mRNA转录水平；酶联免疫吸附试验检测海马炎症因子IL-1β、TNF-α、PGE₂及IL-10含量的变化。结果：行为学检测结果显示，与正常对照组相比，旷场实验中模型组大鼠水平运动和垂直运动得分降低（P<0.01），糖水偏爱实验中糖水偏爱度显著下降（P<0.01），强迫游泳实验中不动时间明显延长（P<0.01）；分子生物学检测结果显示，模型组大鼠海马内ROS含量显著升高（P<0.01），SOD和CAT的活性显著降低（P<0.01），海马IL-1β、TNF-α、PGE₂和IL-10 mRNA和蛋白水平明显升高（P<0.05，P<0.01）。阿魏酸钠和氟西汀均能不同程度地改善CUMS诱导的上述改变。结论：阿魏酸钠能明显改善CUMS所致的大鼠抑郁样行为，其机制可能与降低海马氧化应激水平和改善炎症反应相关。

Anti-depressant effects of sodium ferulate in rats with depression induced by chronic unpredicted mild stress

OBJECTIVE To investigate the anti-depressant effect of sodium ferulate (SF) in rats with depression caused by chronic unpredictable mild stress (CUMS) as well as the relevant mechanism.METHODS The depression-like rat model was established using chronic unpredicted mild stress.Rats were randomly divided into normal control,CUMS model,CUMS + Fluoxetine (10 mg·kg^-1) and CUMS +SF (50,100,150 mg·kg^-1) groups.Drugs or vehicle were administrated after stress procedures for 21 days.Open field test (OFT),sucrose preference test (SPT) and forced swim test (FST) were used to evaluate the anti-depressant effects of SF.The reactive oxygen species (ROS) level as well as superoxide dismutase (SOD) and catalase (CAT) activities in hippocampus were determined by biochemical methods.IL-1β,TNF-α,PGE₂ and IL-10 expressions were measured by real time qPCR and ELISA analysis.RESULTS Behavioral test indicated that crossing score and rearing score in OFT and sucrose preference index in SPT of model group were significantly lower than those of normal control group (P<0.01,P<0.01),while immobility time in FST was significantly increased (P<0.01).Results of biochemical assess revealed that,compared with those in normal control group,the ROS level increased significantly (P<0.01),the SOD and CAT activities decreased significantly (P<0.01),the mRNA and protein level of IL-1β,TNF-α,PGE₂ and IL-10 increased significantly (P<0.05,P<0.01) in rats of CUMS.Sodium ferulate and fluoxetine ameliorated those changes induced by CUMS.CONCLUSION Sodium ferulate improved the depression like behaviors of rats induced by CUMS,and the mechanism may involve the antioxidant and anti-inflammatory effects.