BACKGROUND： Hypothalamus-pituitary-adrenal （HPA） axis dysfunction has been closely linked to anxiety. Previous studies have shown that Valeriana jatamansi Jones extract exhibits clear anxiolytic effects, but it is ...BACKGROUND： Hypothalamus-pituitary-adrenal （HPA） axis dysfunction has been closely linked to anxiety. Previous studies have shown that Valeriana jatamansi Jones extract exhibits clear anxiolytic effects, but it is unclear about the mechanism underlying regulation of the HPA axis dysfunction in these anxiolytic effects. OBJECTIVE： To observe the effects of Valeriana jatamansi Jones （Zhizhu Xiang） extract on HPA axis function in a rat model of anxiety, and to compare these effects with positive control estazolam. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment was performed at Chengdu University of Traditional Chinese Medicine, China, between February and September in 2006. MATERIALS： Estazolam was purchased from Shanghai Jiufu Pharmaceutical, China; Valeriana jatamansiJones was purchased from the Lotus Pond Market for Chinese Herbal Medicine in Chengdu. It consisted of iridoids and flavonoid components. METHODS： A total of 72 Sprague Dawley rats, aged 2 months, were randomly assigned to 6 groups low-, medium-, and high-dose Valerianajatamansi Jones groups intragastrically injected with 0.3, 0.6, and 0.9 g/kg per day Valerianajatamansi Jones extract, respectively; estazolam group intragastrically injected with 1.5 mg/kg per day estazolam; model and normal groups administered 5 mL physiological saline. Anxiety was established in all groups, except the normal group, through the use of elevated plus-maze test at 7 days following drug administration. MAIN OUTCOME MEASURES： Blood β-endorphin and corticosterone levels were determined using enzyme-linked immunosorbent assay following treatment with ValerianajatamansiJones extract. Expressions of HPA axis-related genes were measured by cDNA microarray. RESULTS： Blood β-endorphin and corticosterone levels were significantly greater in the model group than in the normal group. Compared with the model group, levels decreased with Valeriana jatamansi Jones extract or estazolam treatment, particularly in the low-dose Valeriana jatamansi Jones group （P〈 0.01）. cDNA microarray results demonstrated that corticotropin-releasing hormone and Orexin, which are associated with HPA axis function, were differentially expressed; expression increased in the model group, but decreased in rats treated with Valerianajatamansi Jones extract. CONCLUSION： Valerianajatamansi Jones extract plays a role in regulating HPA axis function in a rat model of anxiety, and this effect was superior to estazolam.展开更多
Objective To study the features of the activity changes of glutamate (GLu ) in the hippocampusand hypothalamus and its effects on the activation of the hypothalamus-pituitary-adrenal axis (HPA ) duringacute cerebral i...Objective To study the features of the activity changes of glutamate (GLu ) in the hippocampusand hypothalamus and its effects on the activation of the hypothalamus-pituitary-adrenal axis (HPA ) duringacute cerebral ischemia (ACI ). Methods: The changes of Glu content, corticotrophin releasing hormone(CRH ) mRNA expression level and adrenocorticotropic hormone (ACTH ) concentration were determinedwith high-performance liquid chromatography (HPLC ) and in situ hybridization in different time intervals after middle cerebral artery occlusion (MCAO) in rats. Results: Glu content was increased rapidly in the hippocampus and hypothalamus 15 min after MCAO and reached the peak (the average Glu content in the hippocarnpus and hypothalamus were 21. 50± 2. 88 mg/g wt and 14. 20±2. 58 mg/g wt respectively) in the lsthour after MCAO and it returned rapidly to the base line level after reperfusion. The Gln content in the hippocampus and hypothalamus went up once more in the 24th hour of reperfusion, remained at a relatively highlevel till the 48th hour of reperfusion and then declined gradually. The expression level of CRH mRNA wasmarkedly enhanced in the temporal cortex, hippocampus and hypothalamus in the lst hour after MCAO andthis condition was kept on till the 96th hour of reperfusion. In the same time, the plasma level of ACTH wasrelatively increased. In the peak stage of reperfusion injury,there was a positive correlation of the Glu contentin the hypothalamus with the number of positive cells of CRH mRNA expression and the plasma level of ACTH. Conclusion: The central CRH system is possible to locate mainly in the limbic system and Gln might beone of the factors to induce excessive excitable stress response of the HPA axis.展开更多
目的:探讨加味逍遥散对不同性别抑郁样大鼠的行为、肝脏组织转录组、下丘脑-垂体-肾上腺(HPA)轴相关基因的表达及性激素水平的调控作用。方法:以利血平腹腔注射构建不同性别抑郁大鼠模型,对照组和模型组、氟西汀组、加味逍遥散组分别予...目的:探讨加味逍遥散对不同性别抑郁样大鼠的行为、肝脏组织转录组、下丘脑-垂体-肾上腺(HPA)轴相关基因的表达及性激素水平的调控作用。方法:以利血平腹腔注射构建不同性别抑郁大鼠模型,对照组和模型组、氟西汀组、加味逍遥散组分别予蒸馏水、氟西汀、加味逍遥散灌胃给药,连续21 d。采用旷场试验检测大鼠抑郁样行为,RNA-seq进行肝脏组织转录组分析,real time RT-PCR检测海马组织的5-羟色胺转运体(5-HTT)、γ-氨基丁酸A型受体(GABA_(A)R)、γ-氨基丁酸B型受体(GABA_(B)R2)、乙酰胆碱脂酶(AChE)、谷氨酸受体(GluR2)mRNA表达水平,酶联免疫吸附试验检测大鼠血清卵泡刺激素(FSH)、雌二醇(E2)、睾酮(T)激素水平。结果:加味逍遥散有效改善雌性、雄性大鼠抑郁样行为(P<0.05);主要调控肝脏组织细胞色素P450(CYP)家族基因转录;显著降低雌性抑郁大鼠GABA_BR2、AChE基因和雄性抑郁大鼠5-HTT、GABA_AR、GABA_BR2、GluR2基因表达水平(P<0.05);显著升高雌性抑郁大鼠FSH、E2和雄性抑郁大鼠T激素水平(P<0.05)。结论:加味逍遥散调控肝脏组织转录组,通过HPA-HPG轴发挥疏肝解郁、养血调经作用,有效改善不同性别大鼠抑郁样行为。展开更多
基金Project of Sichuan Provincial Traditional Chinese Medicine Administration,No.200674Science Foundation of Southwest Jiaotong University,No.2006A10+1 种基金"Key New Drug Innovation" National Science and Technology Major Projects During Eleventh Five-Year Plan,No.2009ZX09103-370Chengdu Science and Technology Major Projects During Eleventh Five-Year Plan,No.09GGZD060SF-012
文摘BACKGROUND： Hypothalamus-pituitary-adrenal （HPA） axis dysfunction has been closely linked to anxiety. Previous studies have shown that Valeriana jatamansi Jones extract exhibits clear anxiolytic effects, but it is unclear about the mechanism underlying regulation of the HPA axis dysfunction in these anxiolytic effects. OBJECTIVE： To observe the effects of Valeriana jatamansi Jones （Zhizhu Xiang） extract on HPA axis function in a rat model of anxiety, and to compare these effects with positive control estazolam. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment was performed at Chengdu University of Traditional Chinese Medicine, China, between February and September in 2006. MATERIALS： Estazolam was purchased from Shanghai Jiufu Pharmaceutical, China; Valeriana jatamansiJones was purchased from the Lotus Pond Market for Chinese Herbal Medicine in Chengdu. It consisted of iridoids and flavonoid components. METHODS： A total of 72 Sprague Dawley rats, aged 2 months, were randomly assigned to 6 groups low-, medium-, and high-dose Valerianajatamansi Jones groups intragastrically injected with 0.3, 0.6, and 0.9 g/kg per day Valerianajatamansi Jones extract, respectively; estazolam group intragastrically injected with 1.5 mg/kg per day estazolam; model and normal groups administered 5 mL physiological saline. Anxiety was established in all groups, except the normal group, through the use of elevated plus-maze test at 7 days following drug administration. MAIN OUTCOME MEASURES： Blood β-endorphin and corticosterone levels were determined using enzyme-linked immunosorbent assay following treatment with ValerianajatamansiJones extract. Expressions of HPA axis-related genes were measured by cDNA microarray. RESULTS： Blood β-endorphin and corticosterone levels were significantly greater in the model group than in the normal group. Compared with the model group, levels decreased with Valeriana jatamansi Jones extract or estazolam treatment, particularly in the low-dose Valeriana jatamansi Jones group （P〈 0.01）. cDNA microarray results demonstrated that corticotropin-releasing hormone and Orexin, which are associated with HPA axis function, were differentially expressed; expression increased in the model group, but decreased in rats treated with Valerianajatamansi Jones extract. CONCLUSION： Valerianajatamansi Jones extract plays a role in regulating HPA axis function in a rat model of anxiety, and this effect was superior to estazolam.
文摘Objective To study the features of the activity changes of glutamate (GLu ) in the hippocampusand hypothalamus and its effects on the activation of the hypothalamus-pituitary-adrenal axis (HPA ) duringacute cerebral ischemia (ACI ). Methods: The changes of Glu content, corticotrophin releasing hormone(CRH ) mRNA expression level and adrenocorticotropic hormone (ACTH ) concentration were determinedwith high-performance liquid chromatography (HPLC ) and in situ hybridization in different time intervals after middle cerebral artery occlusion (MCAO) in rats. Results: Glu content was increased rapidly in the hippocampus and hypothalamus 15 min after MCAO and reached the peak (the average Glu content in the hippocarnpus and hypothalamus were 21. 50± 2. 88 mg/g wt and 14. 20±2. 58 mg/g wt respectively) in the lsthour after MCAO and it returned rapidly to the base line level after reperfusion. The Gln content in the hippocampus and hypothalamus went up once more in the 24th hour of reperfusion, remained at a relatively highlevel till the 48th hour of reperfusion and then declined gradually. The expression level of CRH mRNA wasmarkedly enhanced in the temporal cortex, hippocampus and hypothalamus in the lst hour after MCAO andthis condition was kept on till the 96th hour of reperfusion. In the same time, the plasma level of ACTH wasrelatively increased. In the peak stage of reperfusion injury,there was a positive correlation of the Glu contentin the hypothalamus with the number of positive cells of CRH mRNA expression and the plasma level of ACTH. Conclusion: The central CRH system is possible to locate mainly in the limbic system and Gln might beone of the factors to induce excessive excitable stress response of the HPA axis.
文摘目的:探讨加味逍遥散对不同性别抑郁样大鼠的行为、肝脏组织转录组、下丘脑-垂体-肾上腺(HPA)轴相关基因的表达及性激素水平的调控作用。方法:以利血平腹腔注射构建不同性别抑郁大鼠模型,对照组和模型组、氟西汀组、加味逍遥散组分别予蒸馏水、氟西汀、加味逍遥散灌胃给药,连续21 d。采用旷场试验检测大鼠抑郁样行为,RNA-seq进行肝脏组织转录组分析,real time RT-PCR检测海马组织的5-羟色胺转运体(5-HTT)、γ-氨基丁酸A型受体(GABA_(A)R)、γ-氨基丁酸B型受体(GABA_(B)R2)、乙酰胆碱脂酶(AChE)、谷氨酸受体(GluR2)mRNA表达水平,酶联免疫吸附试验检测大鼠血清卵泡刺激素(FSH)、雌二醇(E2)、睾酮(T)激素水平。结果:加味逍遥散有效改善雌性、雄性大鼠抑郁样行为(P<0.05);主要调控肝脏组织细胞色素P450(CYP)家族基因转录;显著降低雌性抑郁大鼠GABA_BR2、AChE基因和雄性抑郁大鼠5-HTT、GABA_AR、GABA_BR2、GluR2基因表达水平(P<0.05);显著升高雌性抑郁大鼠FSH、E2和雄性抑郁大鼠T激素水平(P<0.05)。结论:加味逍遥散调控肝脏组织转录组,通过HPA-HPG轴发挥疏肝解郁、养血调经作用,有效改善不同性别大鼠抑郁样行为。
