漆黄素对脑缺血再灌注诱导学习记忆损伤及HPA轴的影响

中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (9): 1002-1007.

漆黄素对脑缺血再灌注诱导学习记忆损伤及HPA轴的影响

朱洁瑾，吴湧，叶晓莉，叶华进，王刚，费霏，李晴宇

浙江省杭州市第一人民医院，南京医科大学附属杭州医院药学部，杭州 310006，浙江

收稿日期:2017-01-06 修回日期:2017-02-08 出版日期:2017-09-26 发布日期:2017-09-30
通讯作者: 李晴宇，女，本科，主任药师，研究方向：临床药理学和神经药理学。 Tel：0571-56007191 E-mail：26845176@qq.com
作者简介:朱洁瑾，女，硕士研究生，药师，研究方向：神经药理学。 Tel：0571-56007191 E-mail：88258186@qq.com
基金资助:
杭州市卫生科技项目（201348758）

Effect of fisetin on learning and memory impairment induced by cerebral ischemia reperfusion and HPA axis

ZHU Jiejin, WU Yong, YE Xiaoli, YE Huajin, WANG Gang, FEI Fei

Department of Pharmacy, Hangzhou First People's Hospital, Hangzhou Hospital Affiated to Nanjing Medical University，Hangzhou 310006, Zhejiang, China

Received:2017-01-06 Revised:2017-02-08 Online:2017-09-26 Published:2017-09-30

摘要/Abstract

摘要：

目的: 研究漆黄素对脑缺血再灌注大鼠空间学习记忆能力的影响及其可能机制。方法: 成年雄性SD大鼠随机分为假手术组（Sham）、脑缺血再灌注组（IR）、漆黄素组（10，20和40 mg/kg，p.o.），每组8只。采用四血管阻断法（4VO）建立脑缺血再灌注模型，观察大鼠水迷宫学习记忆能力的改变，通过测定血清皮质酮含量的改变，观察漆黄素的作用。同时采用RT-PCR法研究药物对脑缺血再灌注状态下促肾上腺皮质激素释放激素（CRH）、糖皮质激素受体（GR）表达的影响。结果: IR组大鼠在水迷宫实验中表现出学习记忆能力明显下降（P<0.01），漆黄素（20和40 mg/kg）能明显改善上述现象（P<0.05或P<0.01）；与IR组相比，漆黄素（20和40 mg/kg）能降低血清皮质酮含量（P<0.05），同时漆黄素（40 mg/kg）能逆转缺血再灌注大鼠海马区CRH mRNA表达的增加（P<0.05），同时上调GR mRNA水平（P<0.05）。结论: 漆黄素可逆转脑缺血再灌注对大鼠空间学习记忆损伤，这一作用机制可能与下丘脑-垂体-肾上腺轴（HPA）功能的改变有关。

关键词: 漆黄素, HPA轴, 脑缺血再灌注, 促肾上腺皮质激素释放激素

Abstract:

AIM: To investigate the effect of fisetin on learning memorial ability deficit after cerebral ischemia reperfusion and its possible mechanism. METHODS: Adult male Wistar rats were randomly divided into seven groups: the sham operation, the IR model group, fisetin group（10, 20, 40 mg/kg, p.o.）. The four-vessel occlusion method was used to build rat model of cerebral ischemia reperfusion. All rats were tested for Morris water maze（MWM）. The serum level of corticosterone was detected using the enzyme linked immunosorbent assay. At the end, the expressions of corticotropin releasing hormone (CRH) mRNA and glucocorticoid receptor (GR) mRNA in the hippocampus were analyzed by RT-PCR and semi-quantitative in situ hybridization, respectively. RESULTS:Compared with the sham group, the learning ability of the IR rats decreased significantly (P<0.01), fisetin（20, 40 mg/kg）could improve the ability of learning memory significantly（P<0.05 or P<0.01）. The serum level of corticosterone increased in IR rats, and fisetin（20, 40 mg/kg）could also decline the level of this stress hormone（P<0.05）. At the end, the expression of CRH mRNA in the hippocampus of IR rats was increased and fisetin（40 mg/kg）reversed the expression of this gene（P<0.05）; the GR receptor expressions in the hippocampus was reduced and fisetin（40 mg/kg）reversed these changes in IR rats（P<0.05）.CONCLUSION: Fisetin reverses the learning memory damage after cerebral ischemia reperfusion injury, and the mechanism may be mediated by regulating the function of the hypothalamo-pituitary-adrenal (HPA) axis and the expression.

Key words: fisetin, HPA axis, cerebral ischemia reperfusion, corticotropin releasing hormone

中图分类号:

R965.2

朱洁瑾，吴湧，叶晓莉，叶华进，王刚，费霏，李晴宇. 漆黄素对脑缺血再灌注诱导学习记忆损伤及HPA轴的影响[J]. 中国临床药理学与治疗学, 2017, 22(9): 1002-1007.

ZHU Jiejin, WU Yong, YE Xiaoli, YE Huajin, WANG Gang, FEI Fei. Effect of fisetin on learning and memory impairment induced by cerebral ischemia reperfusion and HPA axis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(9): 1002-1007.

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