摘要
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。
ATM To investigate the effect of hyperin （Hyp） on depressive behavior of rats induced by chronic unpredicted mild stress （CUMS）. METHODS Rats were randomly divided into normal control group, model control group, model ＋ Hyp （5, 10, 15 mg·kg-1） groups and model ＋ fluoxetine （10 mg·kg-1） group as positive control, with n = 10 for each. The depression-like rat model was established using 6 weeks of CUMS. Treatments were given （i.g.） 21 days after CUMS for consecutive 2 1 days. Sucrose preference test （SPT） , open-field test （OFF） and forced swim test （FST） were used to evaluate the anti-depressant effect of Hyp. The antioxidant effect of Hyp was observed by detecting of the reactive oxygen species （ROS） and malondialdehyde （MDA） level as well as superoxide dismutase （SOD） activity in hippocampus; serum levels of corticotrophinreleasing hormone （CRH）, adrenocorticotropic hormone （ACTH） and corticosterone （CORT） combine with protein level of glucocorticoid receptor （GR） were test to observed the effect of Hyp on HPA axis activity. RESULTS The results of behavioral manifestations indicated that sucrose preference index in SFF, crossing score and rearing score in OFF of the model control group were significantly lower than the normal control group （P 〈 0.01 ） , while immobility time in FST was significantly increased （P 〈 0.01 ）. All of these behavioral changes induced by CUMS were ameliorated by treatment with Hyp （10, 15 mg·kg-1） and fluoxetine （10 mg·kg-1） （P 〈 0.05, P 〈 0.01）. Compared with the normal control group, the level of ROS and MDA in hippocampus and serum level of CRH, ACTH and CORT were increased significantly （P 〈 0.01） , while activity of SOD and protein level of GR in hippocampus were decreased significantly （P 〈 0.01）. These effects were reversed by Hyp （ 10, 15 mg·kg-1） and fluoxetine （ 10 mg·kg-1） treatments （P 〈 0.05, P 〈 0.01）. CONCLUSION Hyp possesses antidepressant-like activity in CUMS rat and the mechanism may be related to the antioxidant effect and regulation on hypothalamus- pituitary- adrenal axis activity.
作者
张彦
祝晨蔯
ZHANG Yan ZHU Chen-chen(Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou GUANGDONG 510405, China)
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2017年第3期150-156,共7页
Chinese Journal of New Drugs and Clinical Remedies
作者简介
张彦，女，博士研究生在读，副研究员，主要从事中药新药研究，Phn：86—20—3935—8450，E—mail：zhangyangdpu@163．com；
祝晨蔯，研究员，博士生导师，主要从事中药活性成分及质量评价的研究，Phn：86-20-3935-8450，E-mail：zhuchenchenzyy@163．com
