创伤后应激障碍模型大鼠行为学改变和杏仁核bcl—2、bax的表达

目的:检测创伤后应激障碍(PTSD)动物行为学改变,初步探讨PTSD大鼠杏仁核神经细胞bax、 bcl-2的表达.方法:将Wistar大鼠分为对照组和模型组.采用无连续单一应激(SPS)建立PTSD模型,采用旷场实验(OFT)、拒俘反应实验、Morris水迷宫实验(MWM)等观察实验动物情感行为改变,采用化学发光法测定血清皮质醇浓度,分别应用免疫组织化学方法和RT-PCR检测杏仁核神经元bcl-2、 bax蛋白和mRNA的表达.结果:对照组水迷宫实验逃避潜伏期、血清皮质醇浓度分别为(5.632±1.065)s、 (1.25±0.12)μg/dL,模型组分别为(20.762±3.236)s、 (0.58±0.09)μg/dL,差异均有统计学意义.杏仁核bcl-2、 bax蛋白和mRNA在PTSD后表达升高,bcl-2/bax上调.结论:PTSD大鼠行为学表现符合PTSD主要临床表现;PTSD大鼠杏仁核神经细胞bcl-2/bax上调,可能与PTSD发病机制有关.     

创伤后应激障碍大鼠杏仁核LTP及乙酰胆碱酯酶表达的变化

目的探讨大鼠在创伤后应激障碍(posttraumatic stress disorder,PTSD)杏仁核学习记忆的变化。方法选择正常成年雄性wistar大鼠60只,随机均分为正常对照组和单一连续刺激(SPS)的6h,12h,1d,7d及14d组。应用电生理方法测量各组群体锋电位(population spike,PS)幅值;应用酶组织化学方法检测PTSD对乙酰胆碱酯酶(acetylcholine,AChE)的影响。结果与正常对照组PS幅值增强率(134.03±2.540)%相比,高频刺激后,早期杏仁核逐渐受到抑制,其中1d的变化最显著,PS幅值增强率(65.84±5.246)%降低最明显。7d时PS幅值增强率(152.41±11.125)%升至最高,以后逐渐恢复至正常。AChE活性SPS1d时升至最高,7d时降至最低,以后逐渐向正常恢复。结论创伤后应激障碍急性期大鼠杏仁核受抑制,学习记忆能力降低。     

创伤后应激障碍模型大鼠杏仁核COX及Caspase 3 mRNA表达的变化

目的观察创伤后应激障碍(PTSD)大鼠杏仁核神经元细胞色素氧化酶(COX)及Caspase 3 mRNA的表达变化,进一步认识PTSD行为异常的神经生物学机制。方法采用国际认定的连续单一刺激(single prolonged stress,SPS)方法建立大鼠PTSD模型,取成年健康雄性Wister大鼠40只,随机均分为PTSD模型的1d、4d、7d组及正常对照组。应用酶组化检测COX的表达,采用逆转录-聚合酶链式反应(RT-PCR)技术检测细胞色素氧化酶II亚基(COII)及Caspase 3 mRNA在PTSD杏仁核神经元的表达。结果PTSD大鼠杏仁核神经元细胞质内COX活性和COII mRNA表达水平明显低于正常对照组,SPS7d时最低。Caspase 3 mRNA表达于SPS刺激后逐渐上调,于SPS7d时表达最高。结论创伤后应激障碍模型大鼠杏仁核COX,COII及Caspase 3可能与PTSD的发病机制有关。     

PKCζ和PKMζ在创伤后应激障碍大鼠杏仁核的表达

目的探讨创伤后应激障碍(PTSD)大鼠杏仁核PKMζ的表达变化。方法采用单程长时应激(SPS)制备PTSD大鼠模型,将PTSD大鼠分为3组:SPS3d、SPS7d和SPS14d组,正常饲养大鼠作为对照组。取材各组大鼠杏仁核,利用Western blot和免疫荧光染色检测PKMζ蛋白在大鼠杏仁核表达。结果免疫荧光染色结果显示,SPS7d、SPS14d组大鼠杏仁核PKCζ阳性细胞百分数明显多于正常对照组。Western blot结果显示,SPS7d、SPS14d组大鼠杏仁核PKCζ和PKMζ蛋白相对表达水平显著高于正常对照组。结论 PKCζ和PKMζ在PTSD大鼠杏仁核过表达提示其可能参与PTSD的发病过程。     

创伤后应激障碍大鼠杏仁核神经元凋亡及三偏磷酸酶活性的变化

目的:研究创伤后应激障碍(PTSD)大鼠杏仁核神经元细胞凋亡及三偏磷酸酶(TMP)活性的变化.方法:成年健康雄性Wistar大鼠50只,随机分为连续单一应激(SPS) 模型的1、 4、 7、 14 d组及正常对照组.应用Annexin V-FITC/PI双标记流式细胞技术定量检测及分析PTSD大鼠杏仁核神经元细胞凋亡率;利用透射电镜观察杏仁核神经元超微结构改变;利用酶组织化学方法检测杏仁核神经元TMP酶活性的变化.结果:SPS后,杏仁核神经元发生了凋亡的特征性形态学改变,杏仁核神经元细胞凋亡率显著增加,TMP酶活性明显比正常对照组增强,均于第4日达高峰.7 d和14 d凋亡率逐渐减少、TMP酶活性减弱.结论:PTSD大鼠杏仁核神经元发生细胞凋亡,凋亡率增加的同时TMP酶活性相应增强,提示TMP酶参与杏仁核神经元凋亡产物的吞噬.     

杏仁核与创伤后应激障碍发病机制的相关性

创伤后应激障碍(PTSD)是指由于异常威胁性或灾难性心理创伤导致延迟出现和长期持续的精神障碍。杏仁核是大脑中的"恐惧中枢",与创伤性记忆和应激时HPA轴的激活联系密切。PTSD患者有强烈的恐惧和惊吓反应,血中糖皮质激素浓度反常低下,下丘脑-垂体-肾上腺轴(HPA)轴调节紊乱。杏仁核可通过糖皮质激素受体(GR)和盐皮质激素受体(MR)调节激活HPA轴,增加糖皮质激素的释放。PTSD导致杏仁核神经元细胞凋亡,凋亡相关基因Bax和Bcl-2比值增大时,神经细胞出现凋亡。PTSD引发杏仁核神经元长时程增强(LTP),杏仁核是恐惧形成和表达的关键中枢。在恐惧条件反射的形成过程中,杏仁核发生LTP,表明LTP是反应PTSD发生机制的重要指标。PTSD引致乙酰胆碱酯酶(AChE)活性降低,乙酰胆碱增多,恐惧增强;PTSD导致杏仁核神经元MR、GR及MR/GR发生改变,激活HPA轴,导致HPA轴调节紊乱。     

突触可塑性损伤与创伤后应激障碍发病的研究进展

创伤后应激障碍(PTSD)发病呈现逐年增高的趋势,患病后导致患者失能,对患者及其家庭产生严重影响,增加沉重负担.然而关于PTSD发病的病理生理学机制尚不清楚,对于其机制的探讨主要集中在恐惧记忆领域.随着近年来研究的深入,大量证据表明突触可塑性(synaptic plasticity)损伤是PTSD发病和临床表现的重要病...     

创伤后应激障碍对心血管系统疾病的影响

创伤后应激障碍(posttraumatic stress disorder,PTSD)是指个体由于经历对生命具有威胁的事件或严重的创伤,导致一系列精神症状长期持续的精神障碍。PTSD可通过交感神经兴奋、下丘脑-垂体-肾上腺轴和肾素-血管紧张素系统引起各种应激激素如茶酚胺、皮质激素、胰高血糖素、肾素等的释放。而心血管系统是多种应激因素作用的首要靶器官,它在应激机体适应调控中具有非常重要的作用。多项研究表明PTSD患者常有心率加快、血压升高、心律失常等心血管系统症状出现。PTSD反应了应激反应系统的异常调节,而这种调节的异常与心血管疾病的发病机理有着一定的关联。     

4-苯基丁酸对创伤后应激障碍大鼠认知能力的影响

目的:观察4-苯基丁酸(4-PBA)对创伤后应激障碍(PTSD)大鼠海马神经元内质网应激(ERS)与凋亡的影响,探讨4-PBA改善PTSD大鼠认知能力的机制。方法:36只成年SD大鼠随机分为正常组、PTSD组和4-PBA+PTSD组,每组12只。PTSD组采用单次延长应激(SPS)构建PTSD大鼠模型,4-PBA+PTSD组从造模次日开始每天于固定时间腹腔注射4-PBA(40 mg/kg),连续给药7 d。Morris水迷宫实验检测各组大鼠的学习记忆能力; Western Blot实验检测各组大鼠海马葡萄糖调节蛋白78(GRP78)、CCAAT增强子结合蛋白同源蛋白(CHOP)及B淋巴细胞瘤-2(Bcl-2)、蛋白激酶R样内质网激酶(PERK)-真核翻译起始因子2α(e IF2α)-活化转录因子4(ATF4)信号通路相关蛋白表达的变化。结果:在Morris水迷宫实验中,与对照组比较,PTSD组大鼠学习记忆能力明显减退(P <0.01);与PTSD组比较,4-PBA+PTSD组大鼠学习记忆功能明显改善(P <0.01)。Western Blot实验结果显示,与对照组比较,PT...     

车祸事件后创伤后应激障碍的研究

目的 :研究车祸事件后创伤后应激障碍的发生情况及特点。方法 :应用中国精神疾病分类方案与诊断标准第二版修订本中的急性应激障碍 (ASR)和创伤后应激障碍 (PTSD)诊断标准 ,对因车祸住我院治疗的 81例患者进行诊断 ,采用症状自评量表 (SCL -90 ) ,艾森克个性问卷 (EPQ)及症状记录表等进行测评。结果 :车祸后 3个月 ,81例中有 33例 ( 4 0 7%)曾经符合ASR诊断标准 ,31例 ( 38 3%)符合PTSD诊断标准。与非PTSD组比较 ,PTSD组SCL -90总分、总均分、阳性项目数、阴性项目数及躯体化、强迫症状、人际关系敏感、抑郁、焦虑、敌对、恐怖、其它因子分均显著高于非PTSD组 (P <0 0 5～ 0 0 1)。PTSD组情绪稳定度倾向不稳定型 ( 38 71%)的比率高于非PTSD组 (P <0 0 1)。与PTSD发病有关的影响因素为EPQ问卷中神经质、L量表及性别。结论 :车祸事件后PTSD并非罕见 ,与性别及个性心理特征有关。     

外源性硫化氢及K_(ATP)通道对大鼠慢性应激结肠高动力的调节

目的:研究外源性硫化氢(hydrogen sulfide,H2S)及ATP敏感性钾通道(ATP-sensitive potassium channels,KATP)在慢性应激结肠高动力中的作用。方法:制作慢性避水应激(water avoidance stress,WAS)和假避水应激(sham water avoidance stress,SWAS)大鼠模型,观察2组大鼠结肠肌条的收缩活性以及硫氢化钠(Na HS)和格列本脲预处理后对2组大鼠结肠肌条收缩影响并计算Na HS的半数抑制浓度(half maximal inhibitory concentration,IC50),使用免疫荧光及Western blotting法观察KATP通道各亚基在结肠中的分布及表达。结果:WAS组结肠肌条收缩活性明显高于SWAS组;Na HS浓度依赖性抑制2组大鼠纵行肌(longitudinal muscle,LM)和环形肌(circular muscle,CM)的收缩;WAS组LM和CM的Na HS IC50分别为0.2033 mmol/L和0.1438 mmol/L,均明显低于SWAS组(P0.01);格列本脲明显增加2组大鼠肌条Na HS IC50(P0.01);Kir6.1、Kir6.2和SUR-2B在2组大鼠结肠固有肌细胞膜均有分布;WAS组(去除黏膜及黏膜下层后)Kir6.1和SUR2B蛋白表达高于SWAS组(P0.01)。结论:H2S外源性供体Na HS对慢性应激结肠高动力具有潜在的治疗作用。KATP通道亚基Kir6.1/SUR2B表达增加可能是慢性应激结肠动力紊乱的一种适应性反应。     

四硫代钼酸铵作为新型硫化氢供体的鉴定及其对皮肤细胞的保护作用

 目的: 本研究旨在检测金属络合物四硫代钼酸铵(ATTM)的硫化氢(H₂S)释放能力并进一步观察其减轻氧化应激诱导的皮肤细胞损伤的作用。方法:反应瓶法检测ATTM在细胞培养基中释放的H₂S,二氯二氢荧光素二乙酸酯或罗丹明123染色结合荧光显微镜照相术分别检测细胞内活性氧簇(ROS)的含量和线粒体膜电位(ΔΨ_m),用试剂盒检测细胞存活率和乳酸脱氢酶(LDH)的释放。结果:与H₂S供体GYY4137类似,ATTM在细胞培养基中可剂量依赖性地释放H₂S。在25~400 μmol/L 的浓度范围内,ATTM处理对人皮肤细胞(HaCaT细胞)的存活率无明显影响(P>0.05)。紫外线照射或外源性给予ROS供体(过氧化氢,H₂O₂)处理均可增加HaCaT细胞内ROS的含量。400 μmol/L H₂O₂处理可明显降低HaCaT细胞的存活率(P<0.01),而在H₂O₂处理前给予ATTM预处理,细胞存活率明显提高,其中在100和200 μmol/L浓度时ATTM具有最好的细胞保护作用(P<0.01)。400 μmol/L H₂O₂处理还可损害细胞的ΔΨ_m和细胞膜并使LDH释放增加(P<0.01)。而在细胞遭受损伤前给予200 μmol/L ATTM预处理可明显改善ΔΨ_m的水平(P<0.05)并抑制LDH从细胞内释放(P<0.01)。结论:ATTM具有释放H₂S的能力并可保护人皮肤细胞对抗氧化应激诱导的损伤效应。     

硫化氢通过抑制自噬减轻心脏停搏后脑损伤

 目的: 观察硫化氢在心肺复苏后脑保护中的作用,并探讨其对神经元细胞自噬的影响。方法: 窒息法建立大鼠心脏停搏模型。72只雄性Wistar大鼠随机分为假手术(sham)组、模型(model)组和硫氢化钠(NaHS)组。自主循环恢复(ROSC)后2 h、4 h、12 h和24 h用Western blot方法检测神经元自噬标志物beclin-1的表达和微管相关蛋白1轻链3(LC3)的转换;ROSC后12 h,用免疫组化方法观察LC3颗粒的表达;透射电镜观察神经元自噬现象;ROSC后72 h,TUNEL染色计数顶叶皮层凋亡神经元。ROSC后24 h、48 h和72 h行神经功能缺损评分(NDS)评价神经功能。结果: ROSC后2 h、4 h、12 h和24 h,model组自噬标志物beclin- 1的表达持续增加,而NaHS组beclin-1的表达先增加,然后逐渐降低(P < 0.05)。自噬标志物LC3 II/I的表达也是同样趋势。免疫组化显示,ROSC后12 h,model组神经元胞浆和胞核LC3颗粒的比例较NaHS组明显增多(P < 0.05)。电镜显示,model组自噬泡明显多于NaHS组及sham组(P < 0.05)。TUNEL染色显示,ROSC后72 h凋亡神经元数量model组明显多于NaHS组及sham组(P < 0.05)。NDS评分显示,NaHS组在各时点神经功能优于model组(P < 0.05)。结论: 硫化氢可以抑制心脏停搏模型大鼠ROSC后神经元自噬,减少神经元凋亡,改善神经功能。     

Smaller volume of anterior cingulate cortex in abuse-related posttraumatic stress disorder

OBJECTIVE: The anterior cingulate cortex (ACC) plays an important role in emotion, and studies in animals have shown changes in ACC structure with early life stress. The purpose of this study was to measure volume of the ACC in PTSD. METHOD: Magnetic resonance imaging (MRI) was used to measure ACC volume in 8 subjects with abuse-related PTSD and 13 healthy subjects without PTSD. ACC volume included Brodmann's area [BA] 24 and 32. RESULTS: Right ACC volume in PTSD patients was significantly smaller than in non-PTSD subjects. CONCLUSION: These results are consistent with smaller ACC volume in PTSD.     

Symptoms of posttraumatic stress disorder and mental health in women who escaped prostitution and helping activists in shelters

PURPOSE: This study compared the mental symptoms, especially symptoms of posttraumatic stress disorder (PTSD), of women who escaped prostitution, helping activists at shelters, and matched control subjects. MATERIALS AND METHODS: We assessed 113 female ex-prostitutes who had been living at a shelter, 81 helping activists, and 65 control subjects using self-reporting questionnaires on demographic data, symptoms related to trauma and PTSD, stress-related reactions, and other mental health factors. RESULTS: Female ex-prostitutes had significantly higher stress response, somatization, depression, fatigue, frustration, sleep, smoking and alcohol problems, and more frequent and serious PTSD symptoms than the other 2 groups. Helping activists also had significantly higher tension, sleep and smoking problems, and more frequent and serious PTSD symptoms than control subjects. CONCLUSION: These findings show that engagement in prostitution may increase the risks of exposure to violence, which may psychologically traumatize not only the prostitutes themselves but also the people who help them, and that the effects of the trauma last for a long time. Future research is needed to develop a method to assess specific factors that may contribute to vicarious trauma of prostitution, and protect field workers of prostitute victims from vicarious trauma.     

创伤后应激障碍大鼠前额叶内侧皮质糖皮质激素受体表达增高

目的 观察创伤后应激障碍（PTSD）大鼠前额叶内侧皮质（mPFC）神经元糖皮质激素受体（GR）表达的变化。 方法 采用单一连续应激(SPS)方法建立PTSD大鼠模型,取成年健康雄性Wistar大鼠90只,随机分为PTSD模型1d、7d、14d、28d和正常对照组。采用免疫组织化学、免疫印迹和RT-PCR方法分别进行各组mPFC神经元GR表达变化的观察及检测,进行图像分析和统计学处理。结果PTSD大鼠mPFC神经元GR的表达高于对照组,SPS后14d最高,SPS后28d恢复性下调,但仍然高于对照组(P<0.05)。结论PTSD模型大鼠经SPS处理后,mPFC区域出现GR表达的增高。     

A theoretical examination of hydrogen sulfide metabolism and its potential in autocrine/paracrine oxygen sensing

Hydrogen sulfide (H₂S) metabolism has been proposed as the oxygen (O₂) sensing mechanism coupling hypoxia to effector responses in a variety of tissues including vascular and chemoreceptor cells. Implicit in this sensing system is a mechanism for regulating intracellular H₂S concentration, presumably through oxidation. However, verification of this mechanism, or any other pathway of H₂S signaling has been hampered by the lack of suitable methods for measuring intracellular concentration and distribution profiles. Here, intracellular H₂S concentration profiles are modeled using simple monoexponential diffusion equations and current knowledge of H₂S biosynthetic and metabolic pathways. The models predict that; (1) while both mitochondrial oxidation and simple diffusion out of the cell can reduce H₂S concentration, the former is considerably more effective as an effector of intracellular H₂S and (2) exogenously applied H₂S may have unanticipated effects on endogenous signaling processes. In addition, these models provide additional support for mitochondrial H₂S oxidation as the key couple in H₂S-mediated O₂ sensing.     

A critical review of psychological treatments of posttraumatic stress disorder in refugees

Despite much research evidence that refugees suffer from elevated rates of posttraumatic stress disorder (PTSD), relatively few studies have examined the effectiveness of psychological treatments for PTSD in refugees. The field of refugee mental health intervention is dominated by two contrasting approaches, namely trauma-focused therapy and multimodal interventions. This article firstly defines these two approaches, then provides a critical review of 19 research studies that have been undertaken to investigate the efficacy of these treatments. Preliminary research evidence suggests that trauma-focused approaches may have some efficacy in treating PTSD in refugees, but limitations in the methodologies of studies caution against drawing definitive inferences. It is clear that research assessing the treatment of PTSD in refugees is lagging behind that available for other traumatized populations. The review examines important considerations in the treatment of refugees. A theoretical framework is offered that outlines contextual issues, maintaining factors, change mechanisms and the distinctive challenges to traditional trauma-focused treatments posed by the needs of refugees with PTSD.     

A meta-analytic review of exposure in group cognitive behavioral therapy for posttraumatic stress disorder

Although the efficacy of exposure is well established in individual cognitive behavioral treatments for posttraumatic stress disorder (PTSD), some clinicians and researchers have expressed concerns regarding the use of in-session disclosure of trauma details through imaginal exposure in group cognitive behavioral therapy (GCBT) for PTSD. Thus, the aim of the present study was to conduct a systematic review of the empirical support for GCBT in the treatment of PTSD and to compare GCBT protocols that encourage the disclosure of trauma details via in-session exposure to GCBT protocols that do not include in-session exposure. Randomized controlled trials that assessed the efficacy of GCBT for PTSD were included in the meta-analysis. A total of 651 participants with PTSD were included in the 12 eligible GCBT treatment conditions (5 conditions included in-group exposure, 7 conditions did not include in-group exposure). The overall pre–post effect size of GCBT for PTSD (ES = 1.13 [SE = 0.22, 95% CI: 0.69 to 1.56, p  .001]). suggests that GCBT is an effective intervention for individuals with PTSD. No significant differences in effect sizes were found between GCBT treatments that included in-group exposure and those that did not. Although the attrition rate was higher in treatments that included exposure in-group, this rate is comparable to attrition rates in individual CBT treatments and pharmacotherapy for PTSD. The results from this meta-analysis suggest that concerns about the potentially negative impact of group exposure may be unwarranted, and support the use of exposure-based GCBT as a promising treatment option for PTSD.