| 雷秀雯,李艳红,黄松翠,等.羟异栀子苷对抑郁大鼠HPA轴的影响及机制研究[J].浙江中医药大学学报,2021,45(9):977-984. |
| 羟异栀子苷对抑郁大鼠HPA轴的影响及机制研究 |
| Effect and Mechanism of Hydroxyisogeniposide on HPA Axis of Depression Rats |
| DOI：10.16466/j.issn1005-5509.2021.09.007 |
| 中文关键词: 抑郁症 羟异栀子苷 下丘脑-垂体-肾上腺轴 海马组织 糖皮质激素受体 下丘脑促肾上腺皮质激素释放激素 大鼠 |
| 英文关键词: depression hydroxyisogeniposide hypothalamic-pituitary-adrenal axis hippocampal tissue glucocorticoid receptor hypothalamic corticotropin releasing hormone rat |
| 基金项目:2017年洛阳市科技计划医疗卫生项目(1724001A-4) |
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| 中文摘要: |
| [目的]探讨羟异栀子苷(hydroxyisogeniposide，HGP)对抑郁大鼠下丘脑-垂体-肾上腺(hypothalamic-pituitary-adrenal，HPA)轴的影响及机制。[方法]60只无特定病原体(specific pathogen free，SPF)级SD雄性大鼠随机分为对照组、抑郁组、HGP低剂量组(10mg·kg-1)、HGP高剂量组(40mg·kg-1)、阳性药组(氟西汀10mg·kg-1)，每组12只。除对照组外，其余组采用慢性不可预见性温和应激法复制抑郁症大鼠模型，造模成功大鼠分别灌胃给药，1次/d，持续2周。末次给药结束，采用糖水偏好实验和旷场实验观察各组大鼠行为学变化，检测各组血浆促肾上腺皮质激素(adrenocorticotropic hormone，ACTH)、皮质酮(corticosterone，CORT)水平，以苏木精-伊红(hematoxylin-eosin，HE)染色法观察各组大鼠海马组织病理学改变，实时荧光定量聚合酶链反应(Real-time fluorescence quantification polymerase chain reaction，Real-time qPCR)和Western blot检测海马区糖皮质激素受体(glucocorticoid receptor，GR)及下丘脑促肾上腺皮质激素释放激素(corticotropin releasing hormone，CRH)mRNA和蛋白表达。[结果]与抑郁组比较，HGP低、高剂量组及阳性药组糖水消耗占比升高，运动格数、修饰次数增多，阳性药组高于HGP高剂量组，HGP高剂量组高于HGP低剂量组(P＜0.05)。与抑郁组比较，HGP低、高剂量组及阳性药组中央格停留时间缩短，血浆ACTH、CORT水平降低，中央格停留时间阳性药组短于HGP高剂量组，HGP高剂量组短于HGP低剂量组，血浆ACTH、CORT水平HGP高剂量组和阳性药组低于HGP低剂量组(P＜0.05)。与抑郁组比较，HGP低、高剂量组、阳性药组海马区GR mRNA和蛋白相对表达量均升高，阳性药组高于HGP高剂量组，HGP高剂量组高于HGP低剂量组(P＜0.05)。与抑郁组比较，HGP低、高剂量组和阳性药组下丘脑CRH mRNA和蛋白相对表达量降低，阳性药组低于HGP高剂量组，HGP高剂量组低于HGP低剂量组(P＜0.05)。[结论]HGP可有效改善抑郁大鼠行为，其抗抑郁机制可能与调控HPA轴有关。 |
| 英文摘要: |
| [Objective]To investigate the effect and mechanism of hydroxyisogeniposide(HGP) on the hypothalamic-pituitary-adrenal(HPA) axis in depressed rats. [Methods] Sixty male specific pathogen free(SPF) SD rats were randomly divided into control group， depression group， HGP low-dose group(10mg·kg-1)， HGP high-dose group(40mg·kg-1) and positive drug group(fluoxetine 10mg·kg-1). Except for control group， the rest of the groups used chronic unpredictable mild stress method to replicate the depression rat model， and the successfully modeled rats were given intragastric administration once a day for 2 weeks. At the end of the last administration， the syrup preference experiment and open field experiment were used to observe the behavioral changes of rats in each group. The plasma adrenocorticotropic hormone(ACTH) and corticosterone(CORT) levels in each group were detected. The histopathological changes of the hippocampus of each group were observed by hematoxylin-eosin(HE) staining. Glucocorticoid receptor(GR) and hypothalamic corticotropin releasing hormone(CRH) mRNA and protein expressions in hippocampus were detected by Real-time fluorescence quantification polymerase chain reaction(Real-time qPCR) and Western blot. [Results] Compared with depression group， the proportion of syrup consumption increased， and the number of exercise grids and modification times increased in the HGP low-dose group， HGP high-dose group and positive drug group， and among them， positive drug group was higher than HGP high-dose group， and HGP high-dose group was higher than HGP low-dose group(P＜0.05). Compared with depression group， HGP low-dose group， HGP high-dose group and positive drug group had shorter central grid residence time， and lower plasma ACTH and CORT levels， and the central grid residence time in positive drug group was shorter than HGP high-dose group， and HGP high-dose group was shorter than HGP low-dose group， plasma ACTH and CORT levels in HGP high-dose group and positive drug group were lower than HGP low-dose group(P＜0.05). Compared with depression group， the relative expression of GR mRNA and protein in hippocampus of HGP low-dose group， HGP high-dose group and positive drug group increased， and positive drug group was higher than HGP high-dose group， and HGP high-dose group was higher than HGP low-dose group(P＜0.05). Compared with depression group， the relative expression of hypothalamic CRH mRNA and protein in HGP low-dose group， HGP high-dose group and positive drug group decreased， and positive drug group was lower than HGP high-dose group， and HGP high-dose group was lower than HGP low-dose group(P＜0.05). [Conclusion] HGP can effectively improve the behavior of depressed rats， and its antidepressant mechanism may be related to the regulation of HPA axis. |
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