杏仁核内去甲肾上腺素在应激激素调控记忆保持过程中的作用(英文)

There is extensive evidence indicating that the noradrenergic system of the amygdala, particularly the baso-lateral nucleus of the amygdala (BLA), is involved in memory consolidation. This article reviews the central hypothesis that stress hormones released during emotionally arousing experiences activate noradrenergic mechanisms in the BLA, resulting in enhanced memory for those events. Findings from experiments using rats have shown that the memory-modulatory effects of the adreno-cortical stress hormones epinephrine and glucocorticoids involve activation of β-adrenoceptors in the BLA. In addition, both behavioral and microdialysis studies have shown that the noradrenergic system of the BLA also mediates the influences of other neuromodulatory systems such as opioid peptidergic and GABAergic systems on memory storage. Other findings indicate that this stress hormone-induced activation of noradrenergic mechanisms in the BLA regulates memory storage in other brain regions.     

β-肾上腺素能受体在乳腺癌发生发展中的作用

β-肾上腺素能受体(β-adrenergic receptors,β-ARs)广泛分布于机体各组织器官中,在调节心脏功能、血管扩张、能量代谢等方面具有重要作用。研究表明,β-ARs在乳腺癌细胞中异常高表达,可通过影响乳腺癌的生长代谢、侵袭转移、血管生成等过程促进乳腺癌的发生和发展。临床研究证实,阻断β-ARs信号传导可改善乳腺癌患者的预后,故β-ARs或可成为治疗乳腺癌的潜在靶点。本文对β-ARs在乳腺癌发生、发展过程中的作用进行综述,为临床治疗及后续研究提供一些参考。     

抑郁型动脉粥样硬化大鼠模型的建立与评价

目的探讨建立抑郁型动脉粥样硬化大鼠模型的实验方法并评价模型的有效性。方法给大鼠喂食高脂饲料,利用慢性不可预见性应激造成抑郁表现,观察动物摄食量的变化,用旷场试验测定动物行为,检测血清学生化指标,HE染色观察腹主动脉和肝组织病变情况。结果与正常组相比,模型组大鼠食物消耗量明显减少(P<0.01);旷场实验中垂直得分、水平得分、总得分均明显降低(P<0.01);肝、脾、胸腺的脏器系数明显减少(P<0.01);血清中总胆固醇(TC)、低密度脂蛋白(LDL)、白蛋白(ALB)、球蛋白(GLB)、碱性磷酸酶(ALP)、丙二醛(MDA)含量明显升高(P<0.01),高密度脂蛋白(HDL)含量明显降低(P<0.01),超氧化物歧化酶(SOD)活性降低(P<0.05);主动脉内膜-中膜明显增厚、内膜单核细胞、巨噬细胞浸润与聚集增多,内膜表层可见脂纹脂斑病变。结论高脂饲料饲养叠加慢性不可预见性应激,可造成大鼠兼具动脉粥样硬化和抑郁两方面的症状,与伴有抑郁症的动脉粥样硬化病人的临床表现有较好的相似性,是较理想的动物模型。     

绿萼梅总黄酮对慢性应激抑郁模型大鼠抑郁行为的影响及机制研究

目的:考察绿萼梅总黄酮对慢性应激抑郁模型大鼠抑郁行为的影响及机制。方法:将60只大鼠随机分为生理盐水组、模型组、氟西汀组(阳性对照,20 mg/kg)和绿萼梅总黄酮低、中、高剂量组(80、160、240 mg/kg),每组10只。除生理盐水组外,其余各组大鼠均采用慢性不可预见性温和应激(CUMS)+孤养法复制抑郁模型,并于造模同时ig相应药物,每天1次,连续28 d。观察大鼠体质量、摄食量的变化及糖水偏爱程度;通过强迫游泳实验、悬尾实验测定大鼠不动时间以及旷场实验测定大鼠中央格停留时间、水平穿越格数、站立次数、修饰次数的变化;并测定末次给药24 h后大鼠血清中肿瘤坏死因子α(TNF-α)、皮质醇、白细胞介素6(IL-6)、5-羟色胺(5-HT)水平。结果:与生理盐水组比较,模型组大鼠的体质量增加值、摄食量、糖水偏爱百分比均降低;强迫游泳和悬尾实验的不动时间延长;旷场实验的中央格停留时间延长、水平穿越格数、站立次数、修饰次数均减少;血清中TNF-α、皮质醇水平升高,IL-6、5-HT水平降低,差异均有统计学意义(P<0.05或P<0.01)。与模型组比较,除绿萼梅总黄酮低剂量组大鼠糖水偏爱百分比、强迫游泳不动时间、旷场实验修饰次数以及绿萼梅总黄酮低、中剂量组大鼠血清中IL-6、5-HT水平改善不明显外,其余各给药组大鼠上述指标均明显改善(P<0.05或P<0.01)。结论:绿萼梅总黄酮能明显改善CUMS诱导的大鼠抑郁行为,其机制可能与抑制炎症反应、调节下丘脑-垂体-肾上腺轴功能有关。     

中枢去甲肾上腺素系统在焦虑/抑郁中作用的研究进展

去甲肾上腺素(NE)是一种重要的单胺类神经递质,广泛作用于不同的脑区调控觉醒和应激反射。去甲肾上腺素皮质系统的基本功能是通过对新奇环境刺激和觉醒状态的注意来平衡警醒和观察行为。中枢去甲肾上腺素系统实质与应激反应系统相关,而焦虑和抑郁的发病机制也涉及去甲肾上腺素系统的失调。中枢NE的     

慢性不可预见性温和应激致抑郁对大鼠肝脏转运多肽mRNA和蛋白表达的影响

目的 研究慢性不可预见性温和应激（chronic unpredicted mild stress,CUMS）致抑郁对大鼠肝脏有机阴离子转运多肽（organic anion transporting polypeptides,Oatps） mRNA和蛋白表达的影响。方法 24只雄性SD大鼠随机分为抑郁模型组和对照组,模型组连续8周给予CUMS,对照组正常饲养。分别于造模前后称量体重、进行糖水偏好实验和旷场实验,并测定大鼠血浆去甲肾上腺素和皮质酮水平以验证抑郁模型的建立。采用实时荧光定量聚合酶链式反应（RT-qPCR）和蛋白质印迹法（Western blotting）分别检测大鼠肝脏Oatp1a1、Oatp1a4和Oatp1b2 mRNA和蛋白表达。结果 与对照组相比,模型组大鼠体重减轻,糖水偏好百分比下降,垂直运动得分和水平运动得分减少,血浆去甲肾上腺素和皮质酮水平升高,肝脏Oatp1a1、Oatp1a4和Oatp1b2 mRNA和蛋白表达下降。结论 CUMS致抑郁下调大鼠肝脏Oatps mRNA和蛋白表达。     

舒肝解郁胶囊对脑卒中后抑郁患者血浆去甲肾上腺素及多巴胺水平的影响简

目的 探讨舒肝解郁胶囊对脑卒中后抑郁(PSD)患者血浆去甲肾上腺素(NE)及多巴胺(DA)水平的影响.方法 随机将60例脑卒中后抑郁患者分为治疗组与对照组各30例.两组均给予临床常规治疗(包括溶栓、抗血小板凝集、脱水、脑保护药和活血化瘀中药治疗等)和早期康复治疗(良肢位、运动疗法、辅以偏瘫治疗仪、针灸和电刺激等),治疗组加用舒肝解郁胶囊,每次2粒(每粒0.36 g),tid,po.在治疗前1周及治疗2,4周末时抽血测血浆NE及DA含量进行比较.并对患者治疗前后汉密尔顿抑郁量表(HAMD)评分比较.结果 治疗组治疗2,4周后HAMD评分为(15.54±1.68),(6.32±1.52)分,对照组分别为(18.97±1.75)和(15.11±1.43)分;治疗组治疗2,4周后NE分别为(0.30±0.03),(0.37±0.02) μmol.L^-1,对照组分别为(0.26±0.04),(0.30±0.03) μmol.L^-1;治疗组治疗2,4周后DA分别为(2.88±0.15),(3.26±0.07) μmol.L^-1,对照组分别为(2.80±0.17),(2.90±0.11) μmol.L^-1,治疗前两组血浆NE及DA的水平比较无明显差异,治疗4周末时,治疗组NE及DA的水平较治疗前提高(P<0.05),也较对照组增加(P<0.05).结论 舒肝解郁胶囊可提高脑卒中后抑郁患者血浆中NE及DA的水平,从而改善抑郁状态.     

病理状态对心肌细胞及心脏成纤维细胞β3-肾上腺素受体表达的影响

目的 观察与心力衰竭相关的不同病理因素刺激下,Sprague-Dawley（SD）乳鼠心肌细胞和心脏成纤维细胞中 β3-肾上腺素受体（β3-AR）表达变化的差异。方法 分离培养 SD乳鼠心肌细胞和心脏成纤维细胞并行免疫荧光鉴定,分别给予血管紧张素Ⅱ（AngⅡ）及去甲肾上腺素（NE）进行刺激,采用实时荧光定量PCR（qPCR）检测心肌细胞肥大相关基因［心钠肽（ANP）、脑钠肽（BNP）、β-肌球蛋白重链（β-MHC）］、心脏成纤维细胞纤维化相关基因［Ⅰ型胶原蛋白（COL-Ⅰ）、Ⅲ型胶原蛋白（COL-Ⅲ）］及2种细胞中β3-AR的mRNA表达。结果 免疫荧光鉴定显示,分离培养的心肌细胞和心脏成纤维细胞均状态良好。AngⅡ和 NE分别刺激 2种细胞 48 h后,心肌细胞中 ANP、BNP、β-MHC和 β3-AR的表达较对照组明显增加;心脏成纤维细胞中 COL-Ⅰ、COL-Ⅲ表达较对照组明显增加,但 β3-AR的表达没有明显变化。结论 参与心力衰竭发生发展的病理因素 AngⅡ和 NE主要引起心肌细胞的 β3-AR表达增加,而不是心脏成纤维细胞。     

基于血浆代谢组学和网络分析研究柴归颗粒的抗抑郁作用机制

本研究整合代谢组学和生物网络分析工具从生物代谢网络角度系统分析柴归颗粒的抗抑郁作用机制。建立慢性不可预见性轻度应激(chronic unpredictable mild stress, CUMS)抑郁大鼠模型,采用基于LC-MS的血浆代谢组学发现柴归颗粒抗抑郁作用的关键代谢物和代谢途径。整合生物网络分析工具对柴归颗粒调节的关键代谢物进行网络分析,聚焦关键代谢通路,挖掘柴归颗粒抗抑郁作用的潜在靶点。结果显示与对照组相比,模型组大鼠血浆中20个代谢物含量有显著差异(P <0.05),柴归颗粒能显著回调二十二碳三烯酸、3-羟基丁酸、4-羟基苯甲醛、鹅去氧胆酸、胆酸、L-谷氨酰胺、乙醇酸、亚油基肉碱、L-酪氨酸、N-乙酰缬氨酸、棕榈酰肉碱和花生四烯酸等12种代谢物。对柴归颗粒调控的关键代谢物进一步网络分析表明花生四烯酸代谢可能是柴归颗粒发挥抗抑郁作用的重要通路,花生四烯酸代谢途径上的CYP2B6、CYP2E1、CYP2C9、CYP2C8、PLA2G6、PTGS2、ALOX15B、PTGS1、ALOX12和ALOX5等10个蛋白为柴归颗粒发挥抗抑郁作用的潜在靶点。本文涉及的动物实验操作均遵...     

美洛昔康对慢性应激大鼠抑郁行为的影响

目的观察美洛昔康对慢性应激大鼠抑郁行为的影响。方法采用慢性温和不可预见性应激(chronic mild un-predictable stress,CUMS)方法建立大鼠抑郁模型。美洛昔康(1、3和5 mg.kg-1)和舍曲林(5 mg.kg-1)在造模完成后灌胃给药,每天1次,连续20 d。旷场实验和强迫游泳实验检测大鼠行为学变化,生化酶学方法检测大鼠海马和皮层超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量变化,酶联免疫吸附法检测大鼠海马和皮层细胞因子白介素(IL)-1β、白介素(IL)-6、肿瘤坏死因子(TNF)-α含量变化。结果与正常组比较,慢性应激大鼠在强迫游泳实验中静止不动的次数增加(P<0.01),旷场实验中水平和垂直运动减少(P<0.05),海马和皮层SOD活性及IL-6含量降低(P<0.05),MDA及IL-1β、TNF-α含量增加(P<0.05)。与模型组比较,美洛昔康能明显改善CUMS大鼠的抑郁行为,升高海马和皮层中SOD活性及IL-6含量(P<0.05)以及降低大鼠海马和皮层MDA及IL-1β、TNF-α含量(P<0.01)。结论美洛昔康对CUMS诱导的大鼠抑郁行为有明显的改善作用,其机制可能与抑制炎症反应和氧化应激有关。     

Raloxifene hydrochloride for breast cancer risk reduction in postmenopausal women

Introduction: Raloxifene is an estrogen receptor modulator which competes with estrogens for binding to the estrogen receptor. Based on the results of the STAR (Study of Tamoxifen And Raloxifene) trial, raloxifene has been approved by the U.S. Food and Drug Administration for the reduction of breast cancer (BC) risk in postmenopausal women at increased risk.

Areas covered: This analysis reviews the activity of raloxifene and the clinical trials for non-BC indications which led to investigate its use as BC preventive agent. We review the trial establishing its efficacy for BC prevention and the meta-analyses including different SERMs for BC prevention.

Expert commentary: Compared with tamoxifen, raloxifene has shown a slightly lower efficacy in reducing BC risk and a better safety profile. Raloxifene also offers to postmenopausal women a benefit in terms of osteoporosis. Future research should investigate its use in premenopausal women and in association with other preventive agents.     

Serum levels of polychlorinated biphenyls in Mexican women and breast cancer risk

The most prevalent female cancer across the world is breast cancer. Current established breast cancer risk factors explain only a fraction of the breast cancer cases diagnosed, and for this reason, other environmental factors have been studied. Exposure to organochlorine compounds has been linked to an increased incidence of breast cancer, although not all data have been consistent. This study was designed to evaluate the relation between polychlorinated biphenyls (PCB) exposure and breast cancer risk in Mexican women. We recruited 140 women from the General Hospital. The cases were 70 newly diagnosed women. We collected environmental and reproductive information by questionnaire. Blood samples were taken for measurement of serum levels of 20 PCB congeners. Risk of breast cancer was found to be positively associated with heavy congeners, age, postmenopausal status, family history of breast cancer and living close to an industrial facility. When PCB were grouped by structure–activity relationships, the risk of breast cancer was positively associated with groups 2b (odds ratio, OR = 1.90, 95% confidence interval, CI, 1.25–2.88), 3 (OR = 1.81, 95% CI 1.08–3.04) and group 4 (OR = 1.57, 95% CI 1.20–2.07). Among postmenopausal women, PCB levels from groups 1a, 2b, and 4 and total PCB were higher in cases, and an association between risk of breast cancer with groups 1a (OR = 7.59, 95% CI 1.1–51.4), 2b (OR = 3.7, 95% CI 1.2–11.2) and 4 (OR = 1.8, 95% CI 1.1–3.1) was found in this group of women. This study showed an association between heavy and potentially estrogenic PCB congeners and breast cancer risk. Copyright © 2011 John Wiley & Sons, Ltd.