Hypothalamic-pituitary-adrenal axis hyperactivity accounts for anxiety-and depression-like behaviors in rats perinatally exposed to bisphenol A

Accumulating studies have proved that perinatal exposure to environmental dose causes long-term potentiation in anxiety/depression-related behaviors in rats. Hyperactivity of the hypothalamic-pituitary-adrenal （HPA） axis is one of the most consistent biological findings in anxiety- and depression-related disorders. The HPA axis is reported to be susceptible to developmental reprogramming. The present study focused on HPA reactivity in postnatal day （PND） 80 male rats exposed perinatally to environmental-dose BPA. When female breeders were orally administered 2 μg/（kg.day） BPA from gestation day 10 to lactation day 7, their offspring （PND 80 BPA-exposed rats） showed obvious anxiety/depression-like behaviors. Notably, significant increase in serum corticosterone and adrenocorticotropin, and corticotropin-releasing hormone mRNA were detected in BPA-exposed rats before or after the mild stressor. Additionally, the level of glucocorticoid receptor mRNA in the hippocampus, but not the hypothalamus, was decreased in BPA-exposed rats. The levels of hippocampal mineralocorticoid receptor mRNA, neuronal nitric oxide synthase and phosphorylated cAMP response element binding protein were increased in BPA-exposed rats. In addition, the testosterone level was in BPA-exposed rats. The results indicate that reprogramming-induced hyperactivity of the HPA axis is an important link between perinatal BPA exposure and persistent potentiation in anxiety and depression.

Effects of repetitive transcranial magnetic stimulation on hypothalamic-pituitary-adrenal axis of patients with depression

Objective： To investigate the effects of sleep electroencephalogram-modulated repetitive transcranial magnetic stimulation （SEM-rTMS） and conventional rTMS （C-rTMS） on the activity of hypothalamic-pituitary-adrenal （HPA） axis in patients with depression. Methods： In a double-blind, randomized controlled trial, 164 patients diagnosed with depression were randomized to treatment with SEM-rTMS （n=57）, C-rTMS （n=55） or sham rTMS （n=52） for 30 rain every day for 10 d. Before and after treatment plasma concentrations of adrenocorticotropic hormone （ACTH） and cortisol （CORT） were measured, and the 24-item Hamilton Depression Rating Scale （HAMD-24） was used for assessment. Results： The HAMD-24 scores and plasma ACTH and CORT concentrations of these depressive patients before treatment were significantly different from those of the normal control group （P〈0.05）. The HAMD-24 scores and plasma ACTH and CORT concentrations in the SEM-rTMS group and conventional rTMS group were decreased significantly （P〈0.05）. There was a significant positive correlation between the HAMD-24 scores and plasma ACTH （n=240, r=0.105, P=0.048） and CORT concentrations （n-240, r=0.126, P=0.023） in the patients with depression before and after treatment. Conclusion： The antidepressant effect of rTMS, including SEM-rTMS, may be related to its decreasing HPA axis activity. （This trail was registered. No： ChiCTR-TRC-00000465）

Shizhenqing granule stimulates the hypothalamic-pituitary-adrenal axis and reduces serum pro-inflammatory factors in a rat model with chronic eczema

Objective:In this study,we examined the effects of Shizhenqing granule(SZQG)on hypothalamicpituitary-adrenal(HPA)axis and serum inflammatory factors in a rat model of chronic eczema,in order to explore the mechanism of action of SZQG in treatment of this disease.Methods:Sixty SpragueeDawley male rats were randomly divided into six groups(with 10 rats per group):blank group;model group;positive control group(prednisone);and the low-,medium-,and high-dose SZQG groups.Except for the blank group,rats in all other groups were treated with 2,4-dinitrochlorobenzene to induce chronic eczema.These rats were administered prednisone or SZQG for 7 consecutive days after successful establishment of the chronic eczema model,and samples were collected 12 h after the last administration.The degree of skin lesions and the changes in serum levels of corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),cortisol(CORT),interleukin(IL)-4,interferon(IFN)-g,IL-25,and IL-31 among the groups were compared.Results:SZQG effectively increased the levels of CRH,ACTH,and CORT,which decreased in the serum of rats with chronic eczema,stimulated the function of the HPA axis,and promoted the expression of glucocorticoids.SZQG reduced the serum levels of inflammatory factors including IL-4,IL-25 and IL-31,which were overexpressed in rats with chronic eczema,and increased those of anti-inflammatory factor IFN-g,thereby alleviating the inflammatory symptoms and itching,and ameliorating the clinical symptoms of chronic eczema.Conclusion:SZQG effectively alleviates skin lesions in the chronic eczema rat model by stimulating the function of the HPA axis.

The total flavonoids extracted from Xiaobuxin Tang reverse the hyperactivity of hypothalamic-pituitary-adrenal axis in chronically stressed rats

Objective To investigate the effect of XBXT-2 on the activity of hypothalamic-pituitary-adrenal(HPA)axis in chronic mild stress(CMS)model of rats.Methods Using ELISA to test the serum corticosterone,adrenocorticotropic hormone(ACTH)and corticotropin-releasing hormone(CRH)level in CMS rats;Using western blot to determine hippocampal glucocorticoids receptors(GR)expression in CMS rats.Results Co-administration of XBXT-2(25,50 mg·kg-1,p.o.,28 days,the effective doses for behavioral responses)significantly decreased the serum corticosterone and ACTH level in CMS rats,while the CRH level was not markedly affected by chronic stress or drugs.Moreover,XBXT-2 significantly increased the GR expression in the hippocampus of CMS rats.The same effects were observed in the positive control drug imipramine(10 mg·kg-1,p.o.).Conclusions The decrease of serum corticosterone and ACTH level,as well as the increase of hippocampal GR expression may be the mechanisms underlying the antidepressant action of XBXT-2,which may associate with HPA axis.

Seasonal photoperiodic influence of pineal melatonin on hypothalamic-pituitary-adrenal axis-hippocampal-receptor in male rats

Background: Based on the effect of seasonal changes on human visceral function, this study investigated the impact of seasonal photoperiod of the pineal body on hypothalamic-pituitary-adrenal axis-hippocampal-receptor in rats, aiming to reveal the mechanism by which pineal gland melatonin regulates the seasonal secretion of hippocampal neurotransmitters.Methods: Vernal equinox, summer solstice, autumn equinox, and winter solstice were selected as four experimental time points, and rats were randomly divided into normal control group, sham operation group, and pinealectomized group. The seasonal changes in corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH), corticosterone, hypothalamic melatonin receptor(MTR), and hippocampal corticosterone receptor(CORTR) were examined by enzyme-linked immunosorbent assay.Results: Comparing the same group between different seasons, we showed that in the normal control group, CRH, ACTH, corticosterone, and MTR were higher, while CORTR was lower in autumn and winter than in spring(all P <.05). Compared with the normal control group, the pinealectomized group showed higher levels of corticosterone(P =.01), MTR(P =.01), and CORTR(P =.03) during spring;reduced levels of MTR and CORTR(both P <.001) during summer;higher levels of ACTH(P =.001) and MTR(P <.001),and lower levels of CRH(P =.001), corticosterone(P <.001), and CORTR(P =.003) during autumn;and lower levels of CRH(P <.001) and MTR(P =.004), and higher level of ACTH(P <.001) in winter.Conclusions: Seasonal photoperiod acts on the pineal gland to secrete different levels of melatonin,resulting in seasonal changes in the hypothalamic-pituitary-adrenal axis-hippocampal-receptor, which may be the pathophysiological basis for the onset of seasonal affective disorder.

Individual Differences in Stress Responsiveness of the Hypothalamic-Pituitary-Adrenal Axis and Its Vasopressinergic Regulation in Old Monkeys

Stress adaptation is fundamental for health, and the hypothalamic-pituitary-adrenal axis (HPA) is one of its main mechanisms. Considerable data indicate that arginine vasopressin (AVP) related disturbances of stress adaptation can occur with aging. However, most studies of such kind have been performed on rodents, give contradictory results and fail to consider individual characteristics of the animals. The purpose of this study was to investigate individual HPA responsiveness to acute stress and its vasopressinergic regulation in old female rhesus monkeys that differ in their behavioral responses to stress. Animals with depression-like or anxiety-like behavior (DAB) responded with higher plasma levels of ACTH and AVP, lower levels of corticosteroids and higher cortisol/DHEAS molar ratios to restraint stress and to insulin-induced hypoglycemia compared with animals with healthy adaptive behavior. AVP and ACTH dynamics were closely correlated in most animals. AVP treatment produced differences in HPA responses similar to those produced by the stressors. The ACTH response to hypoglycemic stress in the DAB animal with highest HPA responsiveness was dramatically reduced by prior administration of a V1b receptor antagonist. These results suggest that the dysfunctions of HPA observed in old animals with DAB are caused by increased tone of the vasopressinergic system in regulation of HPA stress reactivity.

越鞠丸合毓麟珠汤对多囊卵巢综合征不孕症患者脂代谢和HPA轴功能的影响

目的:观察越鞠丸合毓麟珠汤对多囊卵巢综合征(PCOS)不孕症的治疗效果及对脂代谢和下丘脑-垂体-肾上腺轴(HPA)的影响。方法:选取2020年1月至2022年6月该院收治的PCOS不孕症患者100例,按照计算机随机数字分组法分为对照组、观察组,各50例。对照组患者给予常规西药口服,观察组患者在对照组的基础上加用越鞠丸合毓麟珠汤。治疗3个月经周期后对两组患者的临床疗效进行评价,对两组患者治疗前后中医证候表现进行评分,并检测血清脂代谢指标[三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)]、HPA轴相关指标[卵泡刺激素(FSH)、黄体生成素(LH)、促肾上腺皮质激素(ACTH)和生长激素(GH)]水平,观察两组患者成熟卵泡数、宫颈黏液评分和排卵期子宫内膜厚度的变化。结果:与治疗前比较,两组患者治疗后中医证候评分明显降低,血清TG、TC和LDL-C水平明显降低,血清FSH、LH和ACTH水平明显降低,血清HDL-C、GH水平明显升高,成熟卵泡数、宫颈黏液评分和排卵期子宫内膜厚度均明显增加,差异均有统计学意义(P<0.05);观察组患者中医证候评分、血清脂代谢、HPA轴相关指标和排卵指标的改善均优于对照组,差异均有统计学意义(P<0.05)。观察组患者的临床总有效率为90.0%(45/50),明显高于对照组的76.0%(38/50),差异有统计学意义(P<0.05)。结论:越鞠丸合毓麟珠汤辅助治疗可有效缓解PCOS不孕症患者的症状,提高卵巢功能,调节脂代谢水平和HPA轴功能紊乱,效果较单独应用炔雌醇环丙孕酮片更佳。

HPA轴及海马BDNF与抑郁症的相关性及柴胡经典方治疗研究进展

随着当今时代快速发展,抑郁症已成为人类常见病种,以情绪消沉、沉默寡言、思维迟缓等为主症,严重者甚至有自残、自杀的倾向。抑郁症的发病机制复杂,涉及诸多因素。抗抑郁西药种类多,具有一定的疗效,但存在不良反应大、依从性低及易复发等问题,而中药治疗疗效显著。探讨下丘脑-垂体-肾上腺(HPA轴)、海马脑源性神经营养因子(BDNF)与抑郁症的相关性,对柴胡及其经典复方通过调控HPA轴及海马BDNF发挥抗抑郁作用进行综述,以期为临床研发更多具有抗抑郁作用的中药提供理论参考。

童年期创伤后亲子关系对青少年社会适应的影响:HPA轴系统多基因的调节

童年期的不良经历似乎增加了个体对压力刺激的敏感性,从而可能影响其终身的社会适应。许多研究表明,HPA轴系统基因可能在调节环境因素与社会适应之间发挥作用。然而,过去单个基因与环境相互作用对社会适应的影响存在争议。本研究针对青少年样本(14.15±0.63岁;N=700),采用多位点遗传谱评分(multilocus genetic profile scores,MGPS)计算HPA轴系统多基因得分,利用纵向数据探究其与童年期创伤和亲子关系之间的相互作用,并预测青少年的社会适应(包括抑郁症状、亲社会行为和自伤行为)。研究结果显示,青少年的社会适应(包括抑郁症状和亲社会行为)是遗传(HPA轴系统MGPS)、远端环境(童年期创伤)和近端环境(亲子关系)三者相互作用的结果。随着遗传风险评分的增加,童年期创伤和亲子关系之间的交互作用也增加,这意味着遭受过童年期创伤的个体,亲子关系对社会适应的影响会更加显著,符合差别易感性模型。行为学实验进一步揭示了遗传和环境因素对青少年社会适应的潜在机制。

半枝莲醇提液对2型糖尿病大鼠HPA轴的结构损伤、糖原沉积及相关递质表达的改善作用

【目的】为明确半枝莲醇提液对2型糖尿病(T2DM)及伴其发的下丘脑-垂体-肾上腺轴(HPA轴)亢进的治疗效果,从HPA轴的角度为T2DM提供安全且有效的治疗手段。【方法】选取120只4周龄SPF级Wistar雄性大鼠,随机分为正常饮食组(GD组)24只和高糖高脂饮食组(H组)96只;H组注射STZ诱导T2DM模型,造模成功后随机分为模型对照组(HD组)24只、半枝莲低(SD-L)、中(SD-M)和高(SD-H)剂量组各24只;GD、HD组灌服生理盐水,SD组分别灌服半枝莲醇提液,分别于治疗第5、10、20、30天测定各组大鼠体重、FBG、INS及血脂代谢指标。最后于30 d分别采用H.E、PAS染色法观察HPA轴的组织病理结构及其内糖原数量的变化;醛复红染色法观察胰腺α、β细胞数量的变化;IHC法观察5-HT、GABA分别在下丘脑PVN、VMH中表达的变化。【结果】与GD组相比,HD组发生以下变化:(1)大鼠体重、INS极显著降低,FBG极显著升高。(2)下丘脑PVN和VMH-GE、VMH-GI神经细胞数量减少,神经胶质细胞增多;腺垂体嗜碱性细胞数量减少;肾上腺球状带、束状带萎缩;胰岛萎缩。(3)HPA轴内糖原量均显著或极显著升高。(4)胰岛β细胞坏死、α细胞增多。(5)5-HT、GABA在下丘脑PVN、VMH-GI中的表达量均极显著降低。给药治疗后,这些病理性变化基本得以改善。【结论】半枝莲醇提液对T2DM具有较好的治疗作用,可以缓解T2DM并发的HPA轴内糖原异常沉积及其过度活化。

基于HPG/HPA轴探讨疏肝化瘀法治疗肝郁血瘀型黄褐斑的机制

目的:观察加味桃红四物汤联合珍珠五白面膜治疗对肝郁血瘀型黄褐斑患者HPG/HPA轴的影响,探讨疏肝化瘀法治疗黄褐斑的机制。方法:将90例肝郁血瘀型黄褐斑患者随机分为3组,各30例。基础治疗组予口服加味桃红四物汤治疗,对照组在基础治疗组基础上联合外用氢醌乳膏,观察组在基础治疗组基础上联合外用珍珠五白面膜,3组治疗周期均为8周。对比3组患者治疗前后HPG/HPA轴相关激素水平的变化。结果:治疗后,3组患者LH、E2、FSH、MSH、CORT均下降(P<0.05),且观察组较基础治疗组、对照组改善显著(P<0.05)。结论:加味桃红四物汤联合珍珠五白面膜可明显降低肝郁血瘀型黄褐斑患者的LH、E2、FSH、MSH、CORT水平,提示疏肝化瘀法治疗黄褐斑的作用机制可能是通过调节HPG轴、HPA轴实现的。

自主跑轮运动对小鼠抑郁症与单胺神经递质及HPA轴的影响

为探究自主跑轮运动对小鼠抑郁症与单胺神经递质及下丘脑-垂体-肾上腺轴(HPA)的影响,选取40只C57BL/6J小鼠,随机分成对照组(10只)与抑郁症组(30只)。抑郁症组小鼠采用长期社会击败应激(CSDS)方法建立抑郁症模型,将建模成功的小鼠随机分成抑郁症组(10只)与抑郁症运动组(10只)。抑郁症运动组进行为期3周的自主跑轮运动后,通过旷场及悬尾测小鼠的焦虑样及抑郁样行为,高效液相色谱法测单胺神经递质的变化,酶联免疫吸附测定法测HPA轴的变化。结果表明,与抑郁症组相比,抑郁症运动组旷场中间区域时间百分比显著增加(P<0.05),悬尾不动时间显著减少(P<0.05);海马单胺神经递质中的5-羟色胺(5-HT)、去甲肾上腺素(NE)、多巴胺(DA)含量显著增加(P<0.05);血浆中的HPA轴的促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)及皮质醇(CORT)含量显著下降(P<0.05)。说明自主跑轮运动对于抑郁症小鼠的焦虑及抑郁有改善作用,其作用机制可能与调节单胺神经递质水平及HPA轴功能有关。

Effect of flurbiprofen axetil analgesia after knee replacement on the cytokine contents in serum and joint fluid as well as HPA axis activity

Objective: To investigate the effect of flurbiprofen axetil analgesia after knee replacement on the cytokine contents in serum and joint fluid as well as HPA axis activity. Methods: Patients who underwent knee replacement in People's Hospital of Dongxihu District between April 2015 and January 2018 were selected as the research subjects and randomly divided into the experimental group who accepted flurbiprofen axetil combined with patient-controlled intravenous analgesia and the control group who accepted patient-controlled intravenous analgesia alone. The contents of cytokines and HPA axis-related hormones in serum were measured before surgery as well as 1 d and 3 d after surgery;the contents of cytokines in joint fluid were measured 1 d and 3 d after surgery. Results: Compared with those of same group before surgery, NGF, NPY, TNF-α, IL-2, IL-4, IL-10, ACTH, COR, INS, GH and PRL levels of both groups were increasing 1 d and 3 d after surgery, and NGF, NPY, TNF-α, IL-2, IL-4, IL-10, ACTH, COR, INS, GH and PRL levels in serum as well as PGE2, OPN, TGF-β1, FGF21, CXCL12 and YKL-40 in joint fluid of experimental group 1 d and 3 d after surgery were lower than those of control group. Conclusion: Flurbiprofen axetil analgesia after knee replacement can reduce the release of cytokines in serum and joint fluid, and inhibit the activity of HPA axis, and its analgesic effect is exact.

Central Sensitization of HPA Axis in Modulation of Neuropathic Pain in Diabetic Rats

The present study was designed to investigate the possible role ofHPA （hypothalamic-pituitary-adrenal） axis in neuropathic pain in streptozotocin induced diabetic rats. Wistar albino rats of either sex weighing 180-220 g （n = 6） were employed. Diabetes was induced by administering STZ （streptozotocin） （45 mg/kg, i.p.） once. Neuropathy was induced by the ligation of sciatic nerve in diabetic animals. A glucocorticoid receptor antagonist： ketoconazole 175 mg/kg, p.o. and glucocorticoid receptor agonist： hydrocortisone 1 mg/kg, i.p. were given. Assessment of neuropathic pain was achieved using hot plate and hot immersion tests. Tissue biochemical： lipid peroxidation, NO and glutathione were estimated on 28th day spectrophotometrically. Plasma cortisol level was also estimated using HPLC （high performance liquid chromatography）. Sciatic nerve ligation to diabetic animals caused significant increase in nociceptive responses as hyperalgesia and allodynia, tissue lipid peroxidation and NO products, and decrease in GSH （glutathione） level, in comparison to SC （saline control）. Ketoconazole administration produced decreased pain responses as well as decrease in oxidative stress and inflammatory mediators. Administration of hydrocortisone resulted in suppression of HPA axis. The activation of HPA axis in diabetic animals resulted in significant pain response. This may be due to increased corticosterone level which in turn desensitizes HPA axis and decreased nociceptive response in diabetic animals observed.

布氏田鼠焦虑样行为、反捕食行为及HPA轴水平的性别差异

为探讨布氏田鼠(Lasiopodomys brandtii)焦虑样行为、反捕食行为和下丘脑-垂体-肾上腺(hypothalamic-pituitary-adrenal, HPA)轴水平的性别差异,观测雌雄布氏田鼠在旷场、明暗箱和反捕食箱中的行为差异,及其HPA轴参与调控的促肾上腺激素(adrenalotropic hormone, ACTH)和皮质酮(corticosterone, CORT)水平的差异。结果表明:雄性布氏田鼠在旷场中移动的总距离和平均速度均显著高于雌性,而静止时间显著低于雌性布氏田鼠。雄性布氏田鼠进入明箱的次数与雌性布氏田鼠无显著差异,但在明箱中停留时间显著高于雌性布氏田鼠。暴露于捕食者猫气味时,雌性布氏田鼠仅移动行为的持续时间显著高于雄性布氏田鼠。雌性布氏田鼠血浆中ACTH和CORT浓度显著高于雄性布氏田鼠。综上,布氏田鼠的活动性、焦虑样行为、反捕食行为及HPA轴水平均存在性别差异,提示野生布氏田鼠受其自身内分泌水平的影响,雌雄个体采取截然不同的行为策略以适应当前环境,从而有利于其种群的稳定。

痛泻要方合四逆散颗粒对CUMS诱导的抑郁大鼠HPA轴及PI3K/Akt信号通路的影响

目的:观察痛泻要方合四逆散颗粒对慢性不可预知性温和刺激(CUMS)诱导的抑郁模型大鼠HPA轴及PI3K/Akt信号通路的影响。方法:取48只健康雄性Wistar大鼠,随机分为空白对照组、模型组、低、中、高剂量中药治疗组、西药治疗组,每组8只。除空白对照组外,其余各组均采用CUMS建立抑郁模型。干预4周后取材,酶联免疫吸附测定法测试肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、血清皮质酮(CORT)、去甲肾上腺素(NE)、多巴胺(DA)、5羟色(5-HT)含量;蛋白印迹分析法检测各组大鼠海马磷酸化PI3K、Akt的表达。结果:与空白对照相比,抑郁模型组大鼠CRH、ACTH以及CORT均显著升高,NE、DA以及5-HT均具有显著下降,磷酸化PI3K与Akt蛋白表达量升高,差异有统计学意义(P<0.05);经药物干预后,与模型组相比,中药组CRH、ACTH以及CORT含量均有降低,NE、DA以及5-HT均具有升高,磷酸化PI3K与Akt蛋白表达量下降,差异有统计学意义(P<0.05)。结论:痛泻要方合四逆散颗粒可能通过影响HPA轴及PI3K/Akt信号通路而对抑郁模型大鼠起到积极的防治作用。

基于脑心同治探索冠心Ⅱ号对抑郁模型大鼠海马BDNF及HPA轴的影响

目的观察中药复方冠心II号(GXII)对慢性不可预见性应激(CUMS)大鼠行为学及其对大鼠海马组织脑源性神经营养因子(BDNF),下丘脑-垂体-肾上腺皮质(HPA)轴的影响。方法建立CUMS模型8周后,将CUMS组随机分为模型对照组(MC)、GXII组(GXII)、氟西汀组(F),连同正常组(NC)共计4个组,连续15d灌胃GXII(2.5g·kg^(-1)·d^(-1))、氟西汀(3.5g·kg^(-1)·d^(-1))或等体积0.9%NaCl(5g·kg^(-1)·d^(-1))。采用高效液相色谱法(HPLC)测定大鼠血浆和脑组织中GXII的3种主要活性成分。旷场实验和强迫游泳实验进行行为学检测。Westerm blot测定大鼠海马BDNF,下丘脑促肾上腺皮质激素释放因子(CRF),促肾上腺皮质激素(ACTH)蛋白表达;酶联免疫吸附法(ELISA)测定血清糖皮质激素(GC)表达。结果GXII灌胃大鼠后血清及脑组织中均能测定到羟基红花黄色素A、阿魏酸、丹酚酸B这3种生物活性成分。与MC组大鼠相比,2.5 g/(kg·d)的GXII大鼠在旷场试验中显著增加总距离(P<0.01),缩短强迫游泳试验的不动时间(P<0.01),增加BDNF表达(P<0.01),降低CRF(P<0.05)、ACTH(P<0.01)和GC(P<0.01)的表达。结论GXII能改善CUMS大鼠抑郁样行为的作用,增加大鼠海马BDNF蛋白表达及调节HPA轴可能是其抗抑郁样作用的机制之一。GXII灌胃大鼠后血清及脑组织中测定到的羟基红花黄色素A、阿魏酸、丹酚酸B这3种活性单体成分可能是其抗抑郁作用的潜在物质基础。

加味逍遥散调控HPA-HPG轴对不同性别抑郁模型大鼠的影响

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。

The mechanism of the hypothalamus-pituitary-endocrine axis in anxiety disorder

Anxiety disorder is a common and serious mental disorder.At present,the pathogenesis of anxiety disorder includes hypothalamus-pituitary-adrenal(HPA)axis,neuroimmune,and brain-gut axis disorders,among others.This paper discusses the correlation between anx-iety disorder and the hypothalamus-pituitary-endocrine axis and finds that immune inflammation can be used as a“bridge”between the hypothalamus-pituitary-endocrine axis and anxiety disorder.

穴位埋线对肝郁脾虚证大鼠HPA轴激素的影响

目的:探讨穴位埋线对肝郁脾虚证大鼠血清中下丘脑-垂体-肾上腺(HPA)轴相关激素促肾上腺皮质释放素(CRH)、促肾上腺皮质激素(ACTH)、皮质醇(Cort)含量的影响。方法:根据随机数字表法将30只SD大鼠随机分为正常组10只和造模组20只。采用慢性束缚+过度疲劳+饮食失节法制作肝郁脾虚证大鼠模型,造模成功后再将造模组大鼠随机分为模型组和埋线组,每组10只。埋线组接受双侧太冲、肝俞和脾俞穴位埋线干预,1周1次,共3次,期间观察记录大鼠一般状况。第3次埋线后7天取材并进行指标检测,计算各组大鼠肾上腺指数,采用酶联免疫吸附法(ELISA)检测血清中HPA轴相关激素促肾上腺皮质释放素(CRH)、促肾上腺皮质激素(ACTH)、皮质醇(Cort)浓度。结果:造模成功后,与正常组比较,造模组外观行为积分显著上升,差异有统计学意义(P<0.01)。干预结束后,与正常组比较,模型组大鼠肾上腺指数明显上升,差异有统计学意义(P<0.05),血清CRH、ACTH、Cort含量均明显升高,差异均有统计学意义(P<0.01);与模型组比较,埋线组外观行为积分、大鼠肾上腺指数、血清CRH、ACTH、Cort含量均下降,其中ACTH(P<0.01)、Cort(P<0.05)含量为明显下降,差异均有统计学意义。结论:太冲、肝俞和脾俞穴位埋线能够改善肝郁脾虚证大鼠的症状,其作用机制可能是通过调节HPA轴激素进而纠正HPA轴功能亢进状态。