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

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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。 AIM: To investigate whether sodium ferulate can improve depression-like behavior in chronic unpredicted mild stress (CUMS) rats and to explore its mechanism. Methods: The SD rats were randomly divided into normal control group, CUMS + fluoxetine group (10 mg · kg -1), CUMS + sodium ferulate (50, 100, 150 mg · kg -1) group. The model of chronic depression in rats was established by chronic mild unpredictable stress method. After the model was established, the rats were administered intragastrically for 21 days. Open-field test, sweet-water preference test and forced swimming test. The biochemical methods were used to detect the activity and activity of superoxide dismutase (SOD) and catalase (CAT) in hippocampus of rats Reactive oxygen species (ROS) content. The transcriptional level of IL-1β, TNF-α, PGE2 and IL-10 in the hippocampus were detected by real-time quantitative polymerase chain reaction (q- PGE2 and IL-10 content changes. Results: The results of behavioral tests showed that the scores of horizontal motion and vertical motion of rats in model group were significantly lower than those of control group (P <0.01), and those of sweet water preference test significantly decreased (P <0.01) (P <0.01). The results of molecular biology showed that the content of ROS in hippocampus of model group was significantly increased (P <0.01) and the activities of SOD and CAT were significantly decreased (P < 0.01). The mRNA and protein levels of IL-1β, TNF-α, PGE2 and IL-10 in hippocampus were significantly increased (P <0.05, P <0.01). Both sodium ferulate and fluoxetine could improve CUMS induced changes to some extent. CONCLUSION: Sodium ferulate can significantly improve CUMS-induced depression-like behavior in rats, which may be related to the reduction of oxidative stress in hippocampus and the improvement of inflammatory response.
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