Effects of Ethyl Alcohol Administration to THA Rat Dams During Their Gestation Period on Learning Behavior and on Levels of Monoamines and Metabolites in the Brain of Pups after Birth

Children born from chronic alcoholic mothers have shown behavioral teratogenic effects more frequently than morphological malformations. To investigate the possible mechanisms and evaluate maternal alcohol dosage levels to induce behavioral dysfunctions, we gave pregnant Tokai High Avoider (THA) rats 0, 5,10, and 20% ethanol (EtOH) as drinking water during the gestation period. We evaluated the brain function of pups born of alcohol-administered dams. Sidman avoidance behavior test and the levels of monoamines (nor-adrenalin, dopamine, and serotonin) and metabolites (3,4-dihydroxy-phenyl acetic acid, homovanillic acid, and 5-hydroxyindole acetic acid) in whole brain were examined for neurobehavioral and neurochemical effects. EtOH-exposed THA offsprings showed high pre-and postnatal mortality, growth deficits, and brain weight reductions. Compared with the results of the same conditioning experiment using Wistar rats, the THA rat may have higher susceptibility to the effects of in utero EtOH exposure than Wistar rats. EtOH-exposed THA pups exhibited deficits in avoidance operant learning that were not shown in Wistar rats. We also observed the increased levels of all monoamines that were assumed to be related with the deficit of learning, the decreased levels of 3,4-dihydroxyphenyl acetic acid and homovanillic acid, and the unchanged levels of 5-hydroxyindole acetic acid in pups from dams administered 10 and 20% EtOH. However, contrary alteration of monoamines and their metabolites were shown in pups from 5% EtOH-administered dams.     

益妇散治疗更年期综合征的实验研究

摘 要 目的： 通过观察益妇散的中药复方对去势大鼠血清性激素水平、下丘脑单胺类神经递质的影响,研究其治疗更年期综合征的作用效果。方法: 将60只SD大鼠随机分成5组：假手术组、去卵巢对照组、尼尔雌醇组、益妇散低、高剂量组。连续给药4周,然后测定下丘脑单胺类神经递质,测定血清性激素水平以及测定肾上腺、子宫和胸腺指数等。结果: 益妇散高剂量组去势大鼠的血清E2水平为(4.768±2.548)pmol·L^-1,肾上腺、子宫指数分别为(0.375±0.039)mg·g^-1,（1.572±0.194）mg·g^-1,与去卵巢对照组大鼠的血清E2水平（1.976±0.945）mg·g^-1,肾上腺、子宫指数（0.282±0.039）mg·g^-1,（1.236±0.423）mg·g^-1比较,差异有统计学意义。益妇散高剂量组能够有效地降低去势大鼠异常增高的5 羟色胺硫酸肌肝(5 HT)和5 羟吲哚乙酸(5 HIAA)水平,提高多巴胺(DA)的含量水平,与对照组相比,差异有统计学意义(P<0.01)。结论: 益妇散能够从多方面调节生殖内分泌功能,具有缓解更年期综合征的作用。     

荔枝核皂苷对小鼠学习记忆障碍的改善

目的:探讨荔枝核皂苷对D-半乳糖诱致小鼠学习记忆障碍的改善作用。方法:50只昆明种小鼠完全随机分为正常对照组、模型对照组、石杉碱甲组(0.4 mg/kg·d)、荔枝核皂苷低(15 g/kg·d)和高(60 g/kg·d)剂量组。上述动物除空白对照组外,均皮下(sc)注射D-半乳糖(500 mg/kg·d)8周,并于第5周起分别灌胃相应药物。采用水迷宫和自主活动仪测试小鼠学习和记忆能力,测定血清糖基化;醛糖还原酶活性;采用高效液相库仑阵列电化学检测系统检测人神经氨酸酶(NA)、多巴胺(DA)、5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)二羟苯乙酸(DOPAC)的含量变化。结果:荔枝核皂苷明显改善模型小鼠学习和记忆能力,各给药组与模型对照组相比单胺类递质含量差异无统计学意义(P>0.05)。结论:荔枝核皂苷具有改善D-半乳糖诱致小鼠学习记忆障碍的作用;其作用可能与其减少抑制对脑神经细胞的损伤作用有关。     

艾地苯醌治疗对缺血性脑卒中后抑郁患者血清学指标的影响

目的:研究艾地苯醌治疗对缺血性脑卒中后抑郁患者血清学指标的影响.方法:将本院收治的70例缺血性脑卒中后抑郁患者纳入研究,随机分为两组,观察组接受艾地苯醌治疗,对照组接受安慰剂治疗,比较两组血清中神经细胞因子、单胺类递质以及炎症因子的含量.结果:(1)神经细胞因子:观察组血清脑源性神经营养因子(BDNF)、神经生长因子(NGF)含量高于对照组,差异有统计学意义(P＜0.05);(2)单胺类递质:观察组血清去甲肾上腺素(NE)、5-羟色胺(5-HT)含量高于对照组,5-羟吲哚乙酸(5-HIAA)含量低于对照组,差异有统计学意义(P＜0.05);(3)炎症因子:观察组血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-23(IL-23)含量低于对照组,差异有统计学意义(P＜0.05).结论:艾地苯醌治疗有助于提高神经细胞因子含量、改善单胺类递质代谢、缓解炎症反应,是治疗缺血性脑卒中后抑郁的理想方法.     

6，7-二乙酰黄芩素对大鼠急性肝性脑病的防治作用及机制研究

目的 研究6,7-二乙酰黄芩素对硫代乙酰胺致大鼠急性肝性脑病模型的防治作用及机制。方法 Wistar雄性大鼠60只,随机分为对照组、模型组、乳果糖（阳性药,6 g/kg）组和6,7-二乙酰黄芩素低、中、高剂量（6.25、12.50、25.00 mg/kg）组,每天ig给药1次,连续给药7 d。第5天给药结束后,除对照组外,采用硫代乙酰胺（300 mg/kg）连续ip 2 d建立大鼠肝性脑病模型。观察大鼠状态,考察大鼠肝性脑病评分与死亡率;测定各组大鼠血氨、结肠pH值、血清天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、碱性磷酸酶（ALP）、总胆红素（TBIL）水平;采用苏木素-伊红（HE）染色法观察大鼠肝组织病理学变化;采用ELISA试剂盒法检测大鼠脑组织中γ-氨基丁酸（GABA）、谷氨酸（Glu）、血浆中的5-羟色胺（5-HT）、去甲肾上腺素（NE）的含量;采用Western Blotting试验测定脑组织中GABA-α₁蛋白的表达。结果 造模48 h后,与模型组比较,6,7-二乙酰黄芩素高剂量组大鼠体质量显著升高（P<0.05）,肝性脑病评分显著降低（P<0.05）;各剂量组死亡率均降低;中、高剂量组血清ALT、AST、ALP和TBIL水平均显著降低（P<0.05）;低、中、高剂量组血氨水平显著降低（P<0.05、0.01）;中、高剂量组结肠pH显著降低（P<0.05、0.01）;中、高剂量组大鼠肝脏组织病理学损伤明显改善;各剂量组脑组织中GABA水平显著降低（P<0.01）;中、高剂量组血浆中5-HT水平显著降低（P<0.01）;高剂量组血浆中NE水平显著降低（P<0.01）;高剂量组脑组织中Glu含量显著增加（P<0.01）;高剂量脑组织中GABA-α₁蛋白表达显著降低（P<0.05）。结论 6,7-二乙酰黄芩素对肝脏具有保护作用,对急性肝性脑病具有防治作用,其机制可能与降低血氨、降低结肠pH、调节神经递质水平、抑制相关神经递质受体的表达有关。     

女珍颗粒联合佐匹克隆治疗更年期失眠症的临床研究

目的 探讨女珍颗粒联合佐匹克隆片治疗更年期失眠症的临床疗效。方法 选取2016年3月—2018年10月在内蒙古自治区精神卫生中心进行治疗的82例更年期失眠患者为研究对象,根据用药的差别分为观察组（41例）和对照组（41例）。对照组给予佐匹克隆片,7.5 mg/次,1次/d,睡前服用;观察组在对照组基础上口服女珍颗粒,6 g/次,3次/d。两组均治疗4周后进行效果对比。结果 经治疗,对照组有效率为82.92%,显著低于治疗组95.12%（P<0.05）。经治疗,两组患者匹兹堡睡眠质量指数量表（PSQI）评分降低;多导睡眠监测（PSG）中入睡时间、觉醒时间降低,总睡眠时间增加,睡眠效率提高;睡眠结构中I期时间缩短,II、III期及快速动眼期时间延长（P<0.05）,且观察组睡眠情况显著优于对照组（P<0.05）。经治疗,两组患者血清中神经递质去甲肾上腺素（NE）、5-羟色胺（5-HT）、多巴胺（DA）水平显著升高（P<0.05）,且观察组神经递质水平显著高于对照组（P<0.05）。经治疗,两组焦虑自评量表评分（SAS）、抑郁自评量表评分（SDS）、SCL-90、Hamilton抑郁量表（HAMD）评分均显著降低（P<0.05）,且观察组上述评分显著低于对照组（P<0.05）。结论 女珍颗粒联合佐匹克隆片治疗更年期失眠症效果良好,可有效减轻失眠症状,改善患者负面情绪,提高患者生活质量,有着良好临床应用价值。     

Monoamine oxidases in age-associated diseases: New perspectives for old enzymes

Population aging is one of the most significant social changes of the twenty-first century. This increase in longevity is associated with a higher prevalence of chronic diseases, further rising healthcare costs. At the molecular level, cellular senescence has been identified as a major process in age-associated diseases, as accumulation of senescent cells with aging leads to progressive organ dysfunction. Of particular importance, mitochondrial oxidative stress and consequent organelle alterations have been pointed out as key players in the aging process, by both inducing and maintaining cellular senescence. Monoamine oxidases (MAOs), a class of enzymes that catalyze the degradation of catecholamines and biogenic amines, have been increasingly recognized as major producers of mitochondrial ROS. Although well-known in the brain, evidence showing that MAOs are also expressed in a variety of peripheral organs stimulated a growing interest in the extra-cerebral roles of these enzymes. Besides, the fact that MAO-A and/or MAO-B are frequently upregulated in aged or dysfunctional organs has uncovered new perspectives on their roles in pathological aging. In this review, we will give an overview of the major results on the regulation and function of MAOs in aging and age-related diseases, paying a special attention to the mechanisms linked to the increased degradation of MAO substrates or related to MAO-dependent ROS formation.     

Activation of dopaminergic VTA inputs to the mPFC ameliorates chronic stress-induced breast tumor progression

AimsChronic stress plays an important role in promoting the progression and migration of cancers. However, little is known of any direct impact on tumor progression related to the regulation of emotion‐related circuitry. The aim of this study was to explore the neural‐circuit mechanisms underlying stress‐induced progression of cancers and the impact of emotion‐related regulation of circuitry on tumor growth.MethodsOptogenetic manipulation was applied to unpredictable chronic mild stress (UCMS)–treated mice bearing breast tumor cell. The stress‐related hormones, tumor‐related cytokines, the tyrosine hydroxylase (TH)–positive neurons and their fibers, dopamine receptor–positive cells, and anxiety level were measured using ELISA, immunohistochemical staining, fluorescence in situ hybridization, and behavioral test, respectively.ResultsBy investigating breast cancer mouse models with a chronic mild stress model, optogenetic stimulation, and behavioral analysis, we show that chronic stress induced anxiety‐like behavior in mice and increased serum concentration of norepinephrine and corticosterone, hormones closely related to stress and anxiety. Optogenetic activation of VTA TH terminals in the mPFC rescued anxiety‐like behavior induced by chronic stress. Chronic stress resulted in marked progression of breast tumors, and repetitive optogenetic activation of VTA TH terminals in the mPFC significantly attenuated stress‐induced progression of breast cancers and reduced serum concentration of norepinephrine and corticosterone. Furthermore, there was a positive correlation between serum norepinephrine or corticosterone concentration and tumor size.ConclusionsThese findings indicate a positive role of an emotion regulation circuit on the progression of breast cancer and reveal a link between stress, emotion regulation, and the progression of breast cancers. Our findings provide new insights pertinent to therapeutic interventions in the treatment of breast cancers.     

黄连温胆汤加减对痰热内扰型失眠患者血清单胺类神经递质表达的影响

目的:观察黄连温胆汤加减对痰热内扰型失眠患者血清单胺类神经递质表达的影响。方法:选取2017年1月至2018年12月山东中医药大学附属医院门诊收治的住院患者60例作为研究对象,随机分为对照组和观察组,每组30例。观察组采用黄连温胆汤加减治疗,对照组给予艾司唑仑治疗,疗程4周。治疗后观察患者血清5-HT、DA、NE、GABA的水平,并对患者睡眠脑电图睡眠总时间、REM睡眠时间、睡眠潜伏期、醒觉时间、睡眠效率等参数进行观察。结果:黄连温胆汤加减能上调5-HT、NE、GABA的水平,下调DA的水平,同时对睡眠脑电图睡眠总时间、睡眠潜伏期、醒觉时间、睡眠效率等各指标亦有明显的改善作用(P<0.05或P<0.01)。结论:黄连温胆汤加减对痰热内扰型失眠患者具有明显的治疗作用,其作用机制可能与其调节单胺类神经递质有关。