基于“肝肾失调”探讨阿片类物质心瘾形成的中医病理基础

阿片类物质滥用是目前社会及医学领域的一大难题,其戒断复杂而艰难,关键问题在于阿片类物质心瘾难以戒除。阿片类物质心瘾是指物质滥用者对阿片类物质强烈持久的渴求和难以抑制的用药欲望,其形成的核心机制在于成瘾者对于阿片类物质的异常动机。异常动机的形成在于两个方面,即＂产生动机不良＂以及＂控制不良动机能力下降＂,本研究即从异常动机形成的两个方面切入,通过类比法、引证法及演绎法进行理论研究,分析认为阿片类物质心瘾的形成与肝肾功能的失调相关相关性,研究认为不良动机形成的关键在于阿片类物质引起的肝失疏泄功能的异常,而控制不良动机能力下降则与肝胆主谋略司决断以及肾所藏之志功能的异常相关。     

上海生科院神经所张旭课题组发现调控阿片类物质镇痛作用的新原理

吗啡等阿片类镇痛药是目前临床上最常用、最有效的镇痛药,但一定时期内反复使用这类镇痛药,容易造成耐受（即短期内反复使用阿片类镇痛药,易造成镇痛效果下降,需要逐渐增加用药量）、依赖（成瘾）等副作用。为了开发镇痛效率高、副作用小的新镇痛药,人们急需了解控制阿片类物质的镇痛效率及形成副作用的原理。     

简讯

吗啡等阿片类镇痛药是目前临床上最常用、最有效的镇痛药,但一定时期内反复使用这类镇痛药, 容易造成耐受(即短期内反复使用阿片类镇痛药,易造成镇痛效果下降,需要逐渐增加用药量)、依赖(成瘾)等副作用。为了开发镇痛效率高、副作用小的新镇痛药,人们急需了解控制阿片类物质的镇痛效率及形成副作用的原理。     

阿片依赖及戒断的信号转导机制

药物依赖是一种慢性、复发性的脑疾病,可引起大脑发生病理性变化.在我国滥用的毒品主要是阿片类物质,阿片类物质依赖包括身体依赖(表现为停药后的戒断症状)和精神依赖(表现为满足感和重新用药的渴求).与阿片依赖及耐受相关的因素有内源性阿片肽、阿片受体及其受体后信号转导系统功能状态的适应性改变等.本文就与阿片依赖有关的细胞内信号转导机制作一综述.     

阿片类毒品对HIV-1感染者PBMCs中TLR9基因表达的影响

探讨滥用阿片类毒品(Opiates)对Ⅰ型艾滋病病毒(Human immunodeficiency virus,HIV-1)感染者外周血单个核细胞(PBMCs)中TLR9基因表达水平的影响,为阐明阿片类毒品促进HIV-1复制的作用机制奠定基础。首先在南宁、柳州、钦州市地区的美沙酮、艾滋病自愿咨询检测门诊招募对象,经研究对象知情同意,分为4组,即阿片类毒品滥用的HIV-1感染组(Opiates HIV(+)组)、阿片类毒品滥用非HIV-1感染组(Opiates HIV(-)组)、非阿片类毒品滥用的HIV感染组(Non-opiates HIV(+)组)和健康对照组(Control组),每组随机招募50人。其次,以问卷形式调查对象的人口学特征,并采集其外周静脉血,分离出PBMCs后提取RNA。最后采用qPCR、蛋白质印迹法(Western blot,WB)法检测4组人群PBMCs中TLR9的mRNA、蛋白表达水平。经调查发现4组人群在年龄、性别、民族、户籍所在地、婚姻状况、文化程度和吸毒年限等人口学特征方面差异均无统计学意义(P0.05)。Opiates HIV(+)与Non-Opiates HIV(+)组病毒载量中位数分别为4.450×103和3.977×103 cp/mL,差异有统计学意义(P0.05)。TLR9 mRNA相对表达量在Opiates HIV(+)、Non-Opiates HIV(+)、Opiates HIV(-)和Control组中分别为(2.13±1.59)×10-3、(3.66±2.22)×10-3、(1.96±1.42)×10-3和(7.66±4.87)×10-3。阿片类毒品滥用和HIV感染对TLR9的表达存在交互作用(F=25.91,P=0.000)。经单独效应分析,HIV阳性与阴性人群中,阿片类毒品滥用者TLR9相对表达量均明显低于非毒品滥用者(P0.05);在吸毒人群中,HIV阳性者与HIV阴性者两组间差异没有统计学意义(P0.05);在不吸毒人群中,HIV阳性者低于正常组,两组间差异有统计学意义(P0.05)。WB的结果显示,Opiates HIV(+)、Non-Opiates HIV(+)、Opiates HIV(-)三组TLR9蛋白的表达量均低于Control组。上述结果表明阿片类毒品能够下调HIV-1感染者PBMCs中TLR9的表达水平,提示阿片类毒品可能通过影响TLR9所介导的机体免疫效应,进而促进HIV-1的感染复制。     

突触可塑性与脑疾病的神经发育基础

大脑神经回路高度有序的神经元活动是高级脑功能的基础,神经元之间的突触联结是神经回路的关键功能节点。神经突触根据神经元活动调整其传递效能的能力,亦即突触可塑性,被认为是神经回路发育和学习与记忆功能的基础。其异常则可能导致如抑郁症和阿尔茨海默病等精神、神经疾病。将介绍这两种疾病与突触可塑性的关系,聚焦于相关分子和细胞机制以及新的研究、治疗手段等进展。     

人参皂甙Rg1可改善吗啡依赖大鼠空间学习障碍

长时间应用阿片类制剂如吗啡、海洛因等会诱发脑的适应性改变,从而出现药物成瘾或依赖。以往研究显示,阿片成瘾在许多方面与学习记忆过程类似,相关学者认为是学习的一种异化形式,而这一异化行为的形成是脑内某一记忆系统非适应性回归介导的。另一方面,长时间应用阿片本身也会导致学习记忆能力受损。     

脑力疲劳状态下认知功能损伤研究进展

脑力疲劳是指缺乏动机和警觉的主观感受,一般会出现注意力分散、警觉性降低、情绪低落烦躁、工作绩效下降等现象。认知功能包括注意力、记忆、计算、时空间定向、语言的理解和表达,以及更为高级的能力。认知功能损伤会受到诸多因素的影响,其中脑力疲劳是造成认知损伤的原因之一。本文主要通过该领域的相关研究论文,研究脑力疲劳对注意力、执行功能、情绪和学习记忆四个方面认知功能的影响,以及对脑力疲劳可能引起认知功能损伤的神经生物学机制进行探讨。     

上皮细胞间紧密连接功能的研究进展

紧密连接(tight junction,TJ)广泛存在于所有上皮或内皮细胞间连接的最顶端,是物质经旁细胞途径转运的结构和功能基础。TJ是由跨膜蛋白和胞浆蛋白两大类构成的大分子复合物,主要行使"屏障"和"栅栏"功能,前者可对物质的大小和电荷进行选择,进而调控旁细胞途径的物质转运;后者则通过调控顶膜和基底侧膜两个功能区之间的脂质和蛋白等物质的自由弥散形成高度极性化的细胞。近年来,关于TJ在各种上皮细胞中的作用及调控机制的研究日益增多。本文重点综述了上皮细胞间TJ研究的最新进展,包括TJ的构成、结构和功能检测以及调控机制,并以几类研究比较集中的上皮类型为例介绍TJ研究的现状,这将为防治与TJ改变相关的上皮屏障功能障碍性疾病提供新的思路。     

Forkhead转录因子调控干细胞的命运决定

Forkhead蛋白是一类在进化上高度保守的重要转录因子家族。目前,已经发现超过100种编码Forkhead蛋白的基因,Forkhead蛋白的典型结构特征是含有Forkhead结构域,即一段由100个氨基酸组成的进化上保守的"Forkhead"DNA结合序列。Forkhead蛋白的主要功能包括调控与胚胎发育、细胞生长、增殖、分化、干细胞干性保持、应激反应、语言形成以及长寿相关基因的表达。Forkhead基因的突变或者调控异常会导致发育缺陷以及肿瘤形成。因此,对于不同Forkhead蛋白家族成员功能的深入研究,有助于更好地揭示相关疾病的发病机制,为针对这些疾病的预防和治疗提供理论依据。该文对国内外Forkhead蛋白在干细胞中的主要功能方面的研究成果进行了总结,综述了近年来的最新研究成果。     

Peptides of the "middle molecule" group

The "middle molecules", endotoxins of peptide nature appearing in biological fluids in several diseases, cause the disorder of many regulatory processes, suppress the functions of blood cells, affect the transport characteristics of cell membranes. The review covers different aspects of formation, structure and numerous biological effects of "middle molecules", including the molecular mechanism of their biological action.     

Thyroid hormone effects on the State IV proton motive force in rat liver mitochondria

In order to further investigate the mechanisms regulating the control of mitochondrial respiration by thyroid hormone, the proton motive force was measured during State IV respiration in liver mitochondria isolated from euthyroid, hyperthyroid, hypothyroid and T₃-treated hypothyroid rats. The proton motive force was significantly higher in the hyperthyroid group due to an increased pH. The proton motive force of hypothyroid mitochondria was lower than controls due to a decreased membrane potential. The proton motive force for the T3-treated hypothyroid group did not differ from the euthyroid group due to negating changes in the pH gradient and the membrane potential. The intramitochondrial volume was decreased in the hyperthyroid group and unchanged in the other groups. The results indicate that the thyroid status alters the proton motive force in State IV through individual changes in the pH and membrane potential components of the force. The component that changes in hyperthyroid mitochondria is different from that changing in hypothyroid mitochondria.     

The Role of Voluntary Motivation in the Tolerability of Additional Respiratory Resistance

The role of a processional motivational factor in the tolerability of short-term resistive respiratory loads was studied. The processional motive was formed using the method of moral and material stimulation of a successful activity. The subjects with a material–monetary processional motive were shown to have the greatest tolerability of additional respiratory resistance. They demonstrated the greatest physiological expenditure during the realization of resistive loads. A dissociation between the introspective estimates of processional motives and the values of the subjects' real activity was noted: according to the data of Gerbachevskii's test, the greatest effectiveness of motivation was characteristic of subjects with mobilization of voluntary resources on the basis of moral encouragement and the maximal effectiveness of real activity was observed in subjects with material stimulation motives.     

Alterations in isoforms of glutathione S-transferase in liver and kidney of cadmium exposed rhesus monkeys: Purification and kinetic characterization

Exposure of animals to cadmium (Cd) (25 mg kg-1 body wt day-1) for 10 weeks resulted in preferential accumulation of the metal in liver and kidney. Cd accumulation concomitantly increased zinc (Zn) concentration in both the organs. However, significant decrease in copper level was observed in liver, whereas kidney showed increase in copper (Cu) level. Cd exposure resulted in decreased total GST activity in liver (63%) and kidney (41%) as compared to control group monkeys on normal diet (group I). On isoelectric focusing (IFP) control liver GST segregated into thirteen isoenzymes, while in Cd-treated experimental animals (group II) liver GST resolved into nine isoenzymes. Similarly kidney GST from control animals separated into seven isoenzymes as compared to four isoenzymes from Cd-treated animals. Kinetic analysis showed that Cd exposure did not alter the affinity constant (Km) of GST for GSH and CDNB whereas maximal velocity (Vmax) for these substrates decreased as compared to controls in both the organs, indicating inhibition in GST synthesis by Cd. Cd resulted in a noncompetitive type of inhibition with respect to GSH in vitro. On isoelectric focussing GST of liver and kidney in group II resolved into nine and four isoenzymes as compared to thirteen and seven in group I, showing loss of four basic isoenzymes in case of liver and three isoenzymes in case of kidney. Monkey liver and kidney expressed all the three classes of GST isoenzymes i.e. , µ and , which were serologically identical to human , µ and GSTs. (Mol Cell Biochem 166: 55-63, 1997)     

Implicit motives and gonadal steroid hormones: effects of menstrual cycle phase,oral contraceptive use,and relationship status

Implicit motives for power and affiliation, salivary levels of testosterone, estradiol, and progesterone, and relationship status were measured in 18 normally cycling (NC) women, 18 women using oral contraceptives (OC), and 18 men at three assessments, corresponding to the menstrual, midcycle, and premenstrual phases of women's menstrual cycle. NC and OC women had elevated levels of affiliation motivation and decreased levels of power motivation at midcycle. Power motive changes were particularly pronounced in NC women across cycle phases. OC women and participants not engaged in an intimate relationship had significantly heightened levels of affiliation motivation, averaged across all cycle phases. Testosterone and power motivation, both averaged across all cycle phases, were positively correlated in men and in single women, but not in women engaged in an intimate relationship. Averaged levels of estradiol and power motivation were positively correlated in engaged women, but not in single women or men. Averaged levels of progesterone and affiliation motivation were negatively correlated in men, and there was evidence for a positive association between luteal affiliation motivation and periovulatory and luteal progesterone in NC women. This study therefore provides evidence that implicit motivational states fluctuate across the menstrual cycle, that the power motive is associated with testosterone and, in women, with estradiol, and that the affiliation motive and progesterone are associated in different ways in men and NC women.     

Out of Lust or Jealousy: The Effects of Mate-Related Motives on Study-Time Allocation to Faces Varying in Attractiveness

Although a growing number of empirical studies have revealed that activating mate-related motives might exert a specific set of consequences for human cognition and behaviors, such as attention and memory, little is known about whether mate-related motives affect self-regulated learning. The present study examined the effects of mate-related motives (mate-search and mate-guarding) on study-time allocation to faces varying in attractiveness. In two experiments, participants in mate-related priming conditions (Experiment 1: mate-search; Experiment 2: mate-guarding) or control conditions studied 20 female faces (10 highly attractive, 10 less attractive) during a self-paced study task, and then were given a yes/no face recognition task. The finding of Experiment 1 showed that activating a mate-search motive led the male participants to allocate more time to highly attractive female faces (i.e., perceived potential mates) than to less attractive ones. In Experiment 2, female participants in the mate-guarding priming condition spent more time studying highly attractive female faces (i.e., perceived potential rivals) than less attractive ones, compared to participants in the control condition. These findings illustrate the highly specific consequences of mate-related motives on study-time allocation, and highlight the value of exploring human cognition and motivation within evolutionary and self-regulated learning frameworks.     

Conception of P.V. Simonov about and "altruists" and "egoists" to 80th anniversary of P.V. Simonov (20.04.1926-06.06.2002)

Academician P.V. Simonov is known, first of all, as the founder of "Information theory of requirements and behaviour". He was the first, who declared that requirements are the main original source of behaviour's activity, evolution's regulator, the origin of creation and motive power of individual and collective actions of human beings and animals. In our paper we analyze some positions of Simonov's conception about "agoists" and "altruists", which has the grate practical value and are very actual today.     

Effects of affiliation and power motivation arousal on salivary progesterone and testosterone

Following up on earlier research suggesting a link between implicit affiliation motivation and progesterone (P) and implicit power motivation and testosterone [T; Schultheiss, O.C., Dargel, A., Rohde, W., 2003. Implicit motives and gonadal steroid hormones: Effects of menstrual cycle phase, oral contraceptive use, and relationship status. Horm. Behav. 43, 293-301.], we tested whether arousal of affiliation motivation increases P levels and whether arousal of power motivation increases T levels. Sixty subjects were randomly assigned to watch 30 min of either Bridges of Madison County (affiliation arousal) or The Godfather II (power arousal), or a documentary about the Amazon (control condition). Levels of P and T were assessed in saliva samples taken before (T1), immediately after (T2), and 45 min after the movie (T3). The efficacy of experimental conditions to differentially arouse motives was verified by assessment of changes in affiliation and power motive imagery expressed in imaginative stories written before and after the movie. After the movie, salivary P levels (T2 and T3) in the affiliation-arousal group were significantly higher than in the control group and marginally higher than in the power-arousal group. Subjects' postmovie T responses (T3) depended on premovie T levels: in men, higher premovie T levels predicted a greater likelihood of postmovie T increases in the Power Arousal condition but not in the other conditions, whereas in women, higher premovie T levels tended to be associated with postmovie T decreases in the Power Arousal condition but not in the other conditions. These findings suggest that aroused affiliation motivation has a specific stimulatory effect on P, whereas aroused power motivation has a specific stimulatory effect on T in men, but not in women, with high baseline T levels.     

美洲大蠊化学成分及生物活性的研究进展

美洲大蠊是源自西南民间的传统中药,目前市面已有"康复新液"、"心脉隆注射液"、"肝龙胶囊"和"消癥益肝片"四种相关成药在售。大量临床实践证明,其在抗炎消肿,保肝,组织修复,心肌保护方面有不错的疗效,但是其药理活性的物质基础和作用机制尚不明确,近年来已有不少学者致力于相关的系统研究,并且取得一些进展,从中获得了异黄酮、异香豆素等次生代谢物质,并且认为其机制是多因素,多细胞因子作用的结果。本文将上述的相关成果做了系统介绍,以期对未来美洲大蠊的研究有所帮助。