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目的研究金丝桃苷对慢性温和不可预知应激(CUMS)大鼠抑郁样行为的影响。方法大鼠随机分空白组,模型组,金丝桃苷低(5 mg·kg~(-1))、中(10 mg·kg~(-1))、高(15 mg·kg~(-1))剂量组和氟西汀(10 mg·kg~(-1))对照组,每组10只。采用慢性温和不可预知应激进行为期6周的造模,在造模第3周后给药,持续给药3周。采用糖水偏爱实验、旷场实验和强迫游泳实验观察金丝桃苷的抗抑郁样作用;通过检测海马活性氧(ROS)、丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性观察金丝桃苷的抗氧化应激作用;通过检测血清促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)和皮质酮(CORT)水平以及海马糖皮质激素受体(GR)蛋白表达水平观察金丝桃苷对下丘脑-垂体-肾上腺(HPA)轴的影响。结果与空白组相比,糖水偏爱实验中模型组大鼠糖水偏爱度明显降低、旷场实验中穿越格子数以及直立次数明显减少、强迫游泳试验中不动时间明显增加(均P<0.01),而在给予金丝桃苷中、高剂量以及氟西汀后均能得到不同程度的逆转(P<0.05,或P<0.01);模型组大鼠的海马ROS和MDA含量以及血清CRH、ACTH和CORT水平明显升高、海马SOD活性与GR蛋白表达明显降低(均P<0.01),而在给予金丝桃苷中、高剂量以及氟西汀后均能得到不同程度的逆转(P<0.05,或P<0.01)。结论金丝桃苷能够改善CUMS大鼠的抑郁样作用,其作用与降低海马氧化应激水平及对HPA轴的调节作用相关。
Objective To investigate the effect of hyperin on depression-like behavior in chronic mild unpredictable stress (CUMS) rats. Methods Rats were randomly divided into blank group, model group, low (5 mg · kg -1) hyperin, medium (10 mg · kg -1) and high (15 mg · kg -1) 1)) and fluoxetine (10 mg · kg -1) control group, 10 in each group. Chronic mild unpredictable stress for a period of 6 weeks of modeling, in the model after 3 weeks of administration, continuous administration of 3 weeks. The antidepressant effect of hyperoside was observed by sugar water preference test, open-field test and forced swimming test. The levels of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) Hyperoside, and hyperoside. By detecting serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) and glucocorticoid receptor (GR) The effects of hyperoside on the hypothalamic-pituitary-adrenal (HPA) axis were observed. Results Compared with the control group, the degree of preference for sugar and water in the model group was significantly lower than that in the control group. The numbers of crossing the grid and the number of standing upright in the open-field test were significantly decreased, while the immobility time was significantly increased in the forced swimming test (all P <0.01) The levels of ROS and MDA in the hippocampus of rats in the untreated group were significantly higher than those in the untreated group (P <0.05 or P <0.01) (P <0.05, P <0.01). However, the levels of CORT and Hippocampus SOD and the expression of GR in hippocampus were significantly decreased (all P <0.01) Or P <0.01). Conclusion Hyperin can improve the depression-like effect of CUMS rats, which may be related to the decrease of oxidative stress in hippocampus and the regulation of HPA axis.