目的 探讨长期负性情绪应激对大鼠学习记忆能力的影响,并从海马钙离子( Ca2+)/钙调蛋白( CaM)-钙调蛋白激酶(CaMK)Ⅱ-环腺苷酸反应元件结合蛋白(CREB)信号通路探讨其可能机制.方法 将大鼠分为空白对照组、D-半乳糖(D-gal)脑老化组、负性情绪应激组.通过Morris水迷宫实验检测各组大鼠学习记忆能力,采用高效液相法、荧光免疫染色法和Western印迹方法分别测定海马神经元谷氨酸( glu),Ca2+,N-甲基-D-天冬氨酸受体( NMDAR)、CaM和磷酸化( P)-CREB的含量.结果 与空白对照组相比,D-gal脑老化组和负性情绪应激组Morris水迷宫寻台时间(SPL)均显著延长(P<0. 05);与D-gal脑老化组相比,负性情绪应激组大鼠的SPL无显著差异.与空白对照组相比,D-gal脑老化组和负性情绪应激组海马神经元内glu含量、Ca2+浓度和NMDAR含量均显著增加(P<0. 05),CaM和P-CREB的含量均显著下降(P<0. 05);与脑老化组相比,负性情绪应激组CaM含量显著升高(P<0. 05),其他指标无明显差异.结论 长期负性情绪应激是加速认知衰退进程的重要原因之一,可产生与D-gal相似的认知损伤,其部分机制可能是通过CaM-CaMKⅡ-CREB信号通路,影响学习记忆相关蛋白表达,引起学习记忆能力下降.

Objective To study the effect of Peripateticism pill on the mood, liver depression degree and neuroendocrine function in MCI patients with liver qi stagnation.Methods International diagnostic criteria for MCI and symptoms of liver qi stagnation screening standard were used to screen 40 ~ 65 years old MCI patients with liver qi stagnation.Beck Depression Inventory, Beck Anxiety Inventory and the degree of liver qi stagnation scores table were used to evaluate emotional state and the degree of liver qi stagnation.Enzyme-linked immunosorbent assay (ELISA) was used to analyze adrenocorticotropic hormone (ACTH), glucocorticoid (GC) and norepinephrine (NE) in patients before and after treatment.Results Compared with before treatment, scores of BDI, BAI and symptoms of liver qi stagnation screening were all reduced (P<0.05), ACTH was decreased (P<0.05), NE was increased (P<0.05), GC had no significant changes(P>0.05) after treatment.Conclusions Peripateticism pill could reduce depression, anxiety and symptoms of liver qi stagnation in MCI patients with liver qi stagnation.The possible reason is ACTH concentration decrease and NE concentration increase.

Objective:To study the effect of Shugan method to liver depression degree,cognitive function,8-OHdG,SOD and LPO in MCI patients with liver qi stagnation.Methods:Use the International diagnostic criteria for MCI and symptoms of liver qi stagnation screening standard to screening 40 to 65 years old MCI patients with liver qi stagnation.Use degree of liver qi stagnation scores table to evaluate patients degree of liver qi stagnation.Use MoCA and WAIS-RC to evaluating patients cognitive function.Use ELISA to detect 8-OHdG,SOD and LPO in patients before and after treatment.Results:Compared with before treatment,after treatment in the patients,score of liver qi stagnation symptom reduced,score of visuospatial execution,attention,language,abstract,delayed recall,orientation and total score of MoCA Scale all increased.Score of name of MoCA Scale did not change significantly.Score of similarity,digit span,mapping,block diagram and total score of WAIS-RC all increased.The content of 8-OHdG decreased.The activity of SOD and the content of LPO had no significant change.Conclusion:Shugan method can reduce symptoms of liver qi stagnation in MCI patients with liver qi stagnation,improve patients cognitive function,reduce oxidative damage to DNA is the possible causes of the improve of patients cognitive function.

Objective To explore the effect of MAO A polymorphism on the inhibitory control by ERPs.Methods A total of 36 health of college students were investigated.The amplitudes and latencies of ERP components were studied with a visual Go/Nogo task,and the MAO A polymorphism of the participants was tested by LDR.Results The behavioral data were not different.The amplitudes and laten-cies of N2 component were not different in the three groups.The amplitudes of P3 component of CT group were higher than those of the other two groups.No differences of N2 and P3 waves were found.Conclusions The more cognitive resources are mobilized in CT group than those of the other two groups.

目的：建立并评价负性情绪应激大鼠模型。方法采用改进的不可预知性心理应激诱导方法建立负性情绪应激模型，观察负性情绪应激对大鼠旷场行为活动、糖水消耗量、24 h摄食量的影响，采用ELISA法检测血浆单胺类神经递质水平。结果应激组较空白对照组大鼠的旷场实验水平得分、垂直得分及总得分下降，中央格停留时间增加；糖水消耗量减少，24 h摄食量减少（P＜0．05），血浆促肾上腺皮质激素（ACTH）、皮质酮（CORT）、去甲肾上腺素（NE）水平升高、5－羟色胺（HT）水平下降（P＜0．05）。结论负性情绪应激大鼠模型较好地模拟了人群遭遇多种应激事件产生的负性情绪状态，造模方法成熟可靠。

轻度认知障碍(MCI)是介于正常衰老与痴呆之间的状态,是对认知衰退过速早期干预的最适合阶段.MCI患者常伴情志异常,多为研究者所忽视.益智名方孔圣枕中丹兼具调节情志功效,且已有动物实验和临床研究基础,因此较适合对MCI患者进行干预.而借助fMRI、ERP、MRS等技术,可客观化评测孔圣枕中丹对MCI的疗效并探讨其作用机制.

目的：探讨怒的表达和控制与阿尔茨海默病（Alzheimer＇sdisease；AD）发病关系。方法采用问卷调查，一对一面对面访谈。结果病例组怒的表达显著高于对照组（P＜0．01），而怒的控制显著低于对照组（P＜0．01）。病例组怒表达指数显著高于对照组（P＜0．01）。结论发病前及发病进程中易发怒或郁怒、怒的表达程度高而控制力弱增加了患病的风险。

目的：探讨特质怒与阿尔茨海默病（ AD）发病的关联，初步分析特质怒与怒的表达在 AD 发病进程中的关系。方法采用同性别、同年龄段（±3岁）、同等文化程度1∶1匹配的病例对照研究，问卷调查，面对面访谈。结果病例组特质怒得分高于对照组（t＝44.784，P＝0.000）， OR＝51.857（14.009，191.954）；病例组怒的表达（AX-O、AX-I）显著高于对照组（P＜0.01），病例组和对照组特质怒与怒表达指数均呈正相关（r＝0.579，P＜0.01；r＝0.372，P＜0.01）。结论特质怒倾向高和怒的表达程度高皆是AD发病的危险因素；特质怒与怒的表达在 AD 发病进程中呈正相关，特质怒倾向高且怒的表达程度高更容易诱发AD。

Objective: To discuss the association of tryptophan hydroxylase gene A218C polymorphism and anger started as well as anger expression trait.Methods: After the subjects were selected by STAXI-2 questionnaire,blood of them was sampled,DNA was extracted by phenol-chloroform method,genotyping by PCR-LDR method,and data was statistically analyzed.Results: ①There was no statistical significance of genotype and the allele frequency distribution of the subjects between the high and low trait anger groups.②For high trait anger subjects,there was statistical significance of the following scores of the subjects in three genotype groups(P0.05): anger expression-out(AX-O),anger expression(AX) of female,anger expression-in(AX-I) of male.③For low trait anger subjects,there was statistical significance of the scores of anger expression-in of the subjects in three genotype groups(P0.05).Conclusion: There was the association of TPH gene A218C polymorphism with the following anger traits of normal college students with high trait anger in China: anger expression-out trait,anger expression trait of female,anger expression-in trait of male.The locus polymorphism was also related to the anger expression-in trait of normal college students with low trait anger in China.

<正>人类已疾步跨入老龄化社会,衰老和随之而至的认知功能损害对个人、家庭和社会已构成巨大压力。从战略上考虑,认知功能损害的防治应将重心转向其早期阶段,轻度认知障碍(mild cognitive impairment,MCI)的概念应运而生。初期MCI特指老年人以记忆损害为主,但总体认知功能和日常生活能力正常,没有达到痴呆的状态〔1〕。近年MCI概念的外延扩大,泛指

Objective:To discuss the effects of chronic anger stress on rats' brain aging progress and concentration of plasma monoamine neurotransmitters.Methods:Induced anger stimulation after building D-gal aging and brain aging model,we observed the effects of chronic anger stress on the spatial learning and memory of rats by Morris water maze,and measured the contents of plasma monoamine neurotransmitters:norepinephrine(NE),5-hydroxytryp-tamine(5-HT),dopamine(DA).Results:Compared with the model group,the rats' spatial learning and memory in the angry stress group decreased obviously,the contents of NE and DA in plasma in the angry stress group increased,the contents of 5-HT decreased.Conclusion:The rats' brain aging was aggravated by chronic anger stress,the aging was accelerated;the rat's monoamine neurotransmitters disorder may be one of the mechanisms.

Objective To observe the rat's mitochondrial membrane potential(MMP) and the apoptosis percentage(APOP) of hippocampal neurons,and discuss the effects of chronic anger stress on rats' brain aging.Methods After the rats model with D-gal aging and brain aging affected by anger stress,the effects of chronic anger stress on rats' spatial learning and memory were observed by Morris water maze experiment,and MMP and APOP of rats' hippocampal neurons were measured by flow cytometer.Results Compared with those of model group,the spatial learning and memory of the rats in angry stress group were decreased substantially.In angry stress group,MMP of the rats' hippocampal neurons was decreased(marginal conspicuity),and the APOP of the rats was increased significantly.Conclusions The D-gal brain aging of the rats is aggravated by chronic anger stress,the aging of the rats is accelerated.

Objective To investigate whether anger emotion is the risk factor of Alzheimer′s disease(AD),and for the long-term accumulation of anger can accelerate the aging brain to provide epidemiological basis.Methods AD patients were selected as case groups,the controls without dementia,depression,a history of neurological or psychiatric illness were selected as normal control groups in hospital or community,according to the same sex,same age(± 3 years),and the same educational level,proceeded 1∶1 matched the case-control study.Survey method was face to face interviews.Results Trait anger of AD patients scored significantly higher than that of normal control group(P<0.01).Compared with normal control group, high trait anger individuals risk of AD was significantly higher than that of low trait anger individuals(P<0.01).The OR value(95%CI) was 51.857(14.009,191.954).AD patients with anger expression(AX-O,AX-I) was significantly higher than that of normal control group(P<0.01),and anger control(AC-O,ACI) was significantly lower than that of normal control group(P<0.01),AD patients with anger expression index was significantly higher than that of normal control group(P<0.01).Conclusions Anger emotion is associated with AD,high trait anger is the risk factor of AD.AD patients are more likely to tendency or character of anger expression-out or anger expression-in,they have the high level of anger expression and low controlled anger.

Objective:To investigate the effects and mechanism of anger stress on behavior and memory in the D-gal induced brain aging model rats.Method:Wistar rats were randomly divided into control group,anger model group,D-gal group,anger+D-gal group,and attack rats.The D-galgroup and anger+D-gal group were administered ip 1% D-gal physiological salinesolution(PSS) 10 mL · kg-1 · d-1.The control group and anger model group were ip given the same volume of PSS for 6 weeks.From the third weeks,the anger model group and anger+D-gal group accepted the anger stimulation test for 4 weeks.Each rat in anger model group was placed into one cage and accepted the attack from the invade rat,the tail of invade rat was clamped by using haemostat packed with bandage,two rats bite each other 20 min per day.Morris water maze test was carried out in the 37 days.Six days later all rats were executed and the brain tissue was collected for measurement of superoxide dismutase(SOD),malondialdehyde(MDA),lipofuscin(LPF),meanwhile,pathological changes were observed on cerebral cortex and seahorse.Result:Compared with control group,the behavior and memory significantly decreased(P0.05,P0.01),the brain tissue SOD activity wassignificantly reduced(P0.01) and MDA,LPF content were obviously increased(P0.01) in the anger model group,D-gal group and anger+D-gal group.Furthermore,pathological study showed that the cerebral cortex and seahorsein in the anger model group,D-gal group and anger+D-gal group appeared pathological changes compared with control group,the pathological changes in anger+D-gal group were most obvious.Conclusion:The anger stress has the negatively effects on behavior and memory in the D-gal induced brain aging model rats.

目的探讨阿尔茨海默病（AD）的危险因素,初步分析愤怒情志与AD的关系。方法选取AD患者作为病例,以医院、社区无痴呆病及抑郁症等神经或精神疾病史者为对照,按同性别、同年龄段（±3岁）、同文化程度进行1∶1匹配的病例对照研究。调查方式为面对面访谈。结果单因素分析结果显示,健身锻炼、娱乐活动、家庭和睦、人际关系、AD家族史、脑外伤史、特质怒与AD有统计学关联（P＜0.05）。而吸烟、饮酒、负性生活事件、既往心脑血管病史、既往职业接触史与AD无统计学关联（P＞0.05）。多因素分析结果显示,高特质怒、AD家族史、健身锻炼和娱乐活动与AD有统计学关联（P＜0.05）。结论高特质怒、AD家族史是AD的危险因素,健身锻炼和娱乐活动是AD的保护因素。愤怒情志与AD密切相关,频繁发怒或郁怒等慢性愤怒应激是诱发AD的原因之一。

Objective To establish senescence-accelerated rat model with chronic psychological stress of anger,and evaluate the behavior of rat model.Methods The anger D-gal group was provoked indirectly by clamping aggression mice tails to make anger stress animal model.The morphology of brain tissue and the spatial learning and memory abilities and the open-field experiments were observed.Results Compared with the D-gal group,severe pathological changes of aging in cerebral cortex and hippocampus can be observed in the anger D-gal group rats.The searching platform latency was increased significantly(P<0.05).In openfield experiments,level scores and open-field test scores of the anger D-gal group were increased significantly(P<0.01).The stay time in central lattice was increased significantly(P<0.05).Conclusions Anger stress increases the degenerative changes of the brain and the hippocampus in the D-gal rat,and decreases the spatial learning and memory ability and the cognitive ability.The established model is a relatively ideal senescence-accelerated rat model with long-time psychological stress of anger.

Objective To observe the effect of angry emotion on learning and memory impairment in D-gal induced brain aging rat models.Methods Tail clamp method was used to introduce indirect anger stimulus.Morris water maze test was employed to test the rats' learning and memory abilities. The activities of SOD,MDA,and LPF in brain tissues were tested using nitrite method,thiobarbituric acid colouration method,and fluorescence measurement.HE staining was used to observe the morphology of brain tissue.Results The rats of anger D-gal group swimming in the water maze had a significantly longer duration,the activity of SOD in brain tissues was significantly reduced,but the contents of MDA and LPF were significantly increased.The cerebral cortex became thinner,moreover,granular layer and pyramidal cell layer showed significant atrophy.The number of nerve cells was declined,with the smaller size.The boundary of the nuclear plasma was unclear,and vacuoles were located around the nerve cells.The neuronal cells in hippocampal CA1 were arranged in a loose and fuzzy cell structure,with swelling cell body,pyknosis and deep stained nuclear.Conclusions Angry emotion has promoted the learning and memory dysfunction in the brain aging rat models induced by D-gal,which may be associated with the diminished ability to scavenge oxygen free radicals and the brain damage caused by the declined antioxidant capacity.

Objective To observe the effect of chronic anger stress on the spatial learning and memory ability of D-galactose aging rats, and explain its mechanism from the point of lipid peroxidation and antioxidant.Methods Anger D-gal group were induced indirectly by clamping the aggression mice tails to make anger stress animal model. The effect of chronic anger stress on the spatial learning and memory ability was observed and the plasma SOD activity in serum and the contents of the MDA and LPF in the heart and liver of D-galactose aging rat were tested. The correlation between the levels of plasma SOD and the MDA and LPF in the heart and liver were analyzed. Results Compared with those in D-gal group, the searching platform latency was increased significantly (P＜0.05), the plasma SOD activity in serum of the anger D-gal group was decreased significantly (P＜0.05). The contents of MDA and LPF in the heart and liver were increased significantly (P＜0.05). There was a negative correlation between the levels of plasma SOD and the MDA and LPF in the heart and liver. Conclusions Chronic anger stress inhibits the cognitive function of the aging rats,such as the spatial learning and memory ability,and accelerate the aging process. Its mechanism may be through inhibiting the antioxidation capacity and increasing the lipid peroxidation of heart and liver.

Aim:To investigate the effect of carbamazepine on motor unit potential (MUP) of rectus femoris of rats and the protective effect of Fukang tablets. Methods: A total of 72 rats were randomly allocated into 6 groups.The normal control group was given distilled water,and the other 5 groups were given CBZ for 90 d. At the same time,low GA dose and high-dose Fukang tablet prevention groups were given Fukang tablet at 750 mg/kg and 1 500 mg/kg per day by gavage,and on the 30th d,the low-dose and high-dose Fukang tablet treatment groups were given Fukang tablet.After 90 d,the time course and amplitude of MUP of rectus femoris in the rats were examined. Results: The time course and amplitude of MUP in model group were both lower than those in normal control(P0.05).Compared with model group,the 2 parameters increased in high-dose prevention and treatment groups(P0.05),and only the amplitude of MUP increased in the low-dose prevention and treatment groups(P0.05).Conclusion: Long-term administration of CBZ may injury the muscle,which can be prevented by Fukang tablet.