成年海马神经元再生与抑郁症的机制研究进展

成年海马脑区有持续神经再生,早期研究表明抑郁模型的成年神经再生受损,文中将从抑郁患者海马影像学改变、海马神经再生与抑郁的关系及抗抑郁药物对神经再生的影响几个方面,对抑郁症与成年海马神经再生的研究现状进行概括分析。     

老年非酒精性脂肪肝与慢性代谢性疾病的相关性

目的探讨老年患者非酒精性脂肪肝(NAFL)与血尿酸(UA)等代谢指标的相关性。方法选择2008年1月至2010年12月在北京军区总医院的住院患者427例,年龄67～89(75.3±12.1)岁,男332例,女95例,分为非脂肪肝组和NAFL组,分析两组患者血UA水平和其他代谢指标(转氨酶、血糖、体质量指数、血脂、肾功能及糖尿病、高血压病、冠心病)对其发病的影响。结果两组间比较NAFL组的UA、丙氨酸氨基转移酶(ALT)、血糖、体质量指数(BMI)、三酰甘油(TG)均高于非脂肪肝组;低密度脂蛋白胆固醇(LDL-C)、肌酐(Cr)低于非脂肪肝组;NAFL组糖尿病、冠心病的发病率高,差异均有统计学意义(均P<0.05)。以脂肪肝为因变量,Logistic回归分析显示,糖尿病、吸烟、GPT高、肌酐低、UA高是脂肪肝的危险因素,上述因素均与脂肪肝呈正相关(P<0.05)。结论 NAFL患者的UA、TG、BMI高,糖尿病、冠心病的发病率高;而LDL-C低。预防脂肪肝应重视控制血糖、血压、血脂、体质量、UA等危险因素。     

Angelica tenuissima Nakai Ameliorates Cognitive Impairment and Promotes Neurogenesis in Mouse Model of Alzheimer's Disease

Objective: To research Angelica tenuissima Nakai(ATN) for use in novel Alzheimer's disease(AD) therapeutics. Methods: The effect of a 30% ethanol extract of ATN(KH032) on AD-like cognitive impairment and neuropathological and neuroinflammatory changes induced by bilateral intracerebroventricular injections of β-amyloid(Aβ) peptide(Aβ_(1-42)) was investigated. Male C57 Bl/6 mice were randomly divided into 4 groups, 10 in each group. KH032-treated groups were administrated with a low or high dose of KH032(50 and 200 mg/kg, respectively), intragastrically for 16 days; distilled water was applied in the sham and negative groups. Open field test, Y maze and Morris water maze test were used for behavior test and cognitive ability. In addition, the neuroprotective effects of KH032 in Aβ_(1-42)-infused mice on the histopathological markers [neuronspecific nuclear protein(Neu N), Aβ1-42] of neurodegeneration were examined. The levels of glial fibrillary acidic protein(GFAP), Neu N, phosphorylation extracellular signal-regulated kinase(ERK)/ERK, brain-derived neurotrophic factor(BDNF), phosphorylation c AMP response element-binding(CREB)/CREB protein expression were measured by Western blot. Results: KH032 treatment ameliorated cognitive impairments, reduced the overexpression of Aβ_(1-42), and inhibited neuronal loss and neuroinflammatory response in the Aβ_(1-42)-infused mice. Moreover, KH032 treatment enhanced BDNF expression levels in the hippocampus. Finally, KH032 treatment increased phosphorylation of ERK1/2 and CREB, vital for ERK-CREB signaling. Conclusions: KH032 attenuated cognitive deficits in the Aβ_(1-42)-infused mice by increasing BDNF expression and ERK1/2 and CREB phosphorylation and inhibiting neuronal loss and neuroinflammatory response, suggesting that KH032 has therapeutic potential in neurodegenerative disorders such as AD.     

Angelica tenuissima Nakai Ameliorates Cognitive Impairment and Promotes Neurogenesis in Mouse Model of Alzheimer's Disease

Objective: To research Angelica tenuissima Nakai (ATN) for use in novel Alzheimer''s disease (AD) therapeutics. Methods: The effect of a 30% ethanol extract of ATN (KH032) on AD-like cognitive impairment and neuropathological and neuroinflammatory changes induced by bilateral intracerebroventricular injections of β-amyloid (Aβ) peptide (Aβ1-42) was investigated. Male C57Bl/6 mice were randomly divided into 4 groups, 10 in each group. KH032-treated groups were administrated with a low or high dose of KH032 (50 and 200 mg/kg, respectively), intragastrically for 16 days; distilled water was applied in the sham and negative groups. Open field test, Y maze and Morris water maze test were used for behavior test and cognitive ability. In addition, the neuroprotective effects of KH032 in Aβ1-42-infused mice on the histopathological markers [neuron-specific nuclear protein (NeuN), Aβ1-42] of neurodegeneration were examined. The levels of glial fibrillary acidic protein (GFAP), NeuN, phosphorylation extracellular signal-regulated kinase (ERK)/ERK, brain-derived neurotrophic factor (BDNF), phosphorylation cAMP response element-binding (CREB)/CREB protein expression were measured by Western blot. Results: KH032 treatment ameliorated cognitive impairments, reduced the overexpression of Aβ1-42, and inhibited neuronal loss and neuroinflammatory response in the Aβ1-42-infused mice. Moreover, KH032 treatment enhanced BDNF expression levels in the hippocampus. Finally, KH032 treatment increased phosphorylation of ERK1/2 and CREB, vital for ERK-CREB signaling. Conclusions: KH032 attenuated cognitive deficits in the Aβ1-42-infused mice by increasing BDNF expression and ERK1/2 and CREB phosphorylation and inhibiting neuronal loss and neuroinflammatory response, suggesting that KH032 has therapeutic potential in neurodegenerative disorders such as AD.     

自我效能、情绪稳定性、疲劳与医生抑郁倾向的关系

目的探讨分析一般自我效能感、情绪稳定性、疲劳与医生抑郁倾向的关系,以及对抑郁倾向的交互作用,为改善医生的抑郁倾向状况提供参考依据。方法采用整群随机抽样法,应用流调用抑郁自评量表、一般自我效能感量表、艾森克人格问卷简式量表中文版和疲劳评定量表对河南省郑州市某市级医院455名医生进行横断面调查。结果抑郁倾向与疲劳、情绪稳定性呈中度正相关(r=0.429,0.617,P<0.01),与一般自我效能感呈负相关(r=-0.385,P<0.01)。疲劳、一般自我效能感和情绪稳定性与抑郁倾向的交互作用显著(P<0.05),其中疲劳、情绪稳定性的主效应呈显著正相关(β=1.829、1.654,P<0.001)。结论情绪稳定性是影响疲劳对抑郁倾向作用的主要因素,在经历疲劳时,情绪稳定医生的抑郁倾向始终低于情绪不稳的医生。     

调节ALK5受体活化水平优化间充质干细胞的内皮分化及组织工程血管的应用

【目的】 目前干细胞分化内皮细胞(EC)用于血管治疗受限于分化率,既往研究提示转化生长因子β1(TGFβ1)参与内皮分化的调控,其作用因受体途径及分化阶段而不同?本实验即研究TGFβ1主要Ⅰ型受体ALK5活化水平与间充质干细胞(MSC)的内皮细胞分化效率间的关系及分化内皮细胞应用组织工程血管的研究? 【方法】 采用差速贴壁及流式分选获得大鼠骨髓CD31-MSC,以含VEGF?bFGF及EGM-2的培养基内皮诱导2周组作标准对照组,实验组为分阶段添加TGFβ1活化ALK5组? SB431542抑制ALK5组;免疫荧光检测分化中内皮细胞标志蛋白vWF?KDR动态表达;诱导14 d后通过流式细胞术分析各组CD31+ 百分率比较诱导效率,并检测诱导细胞体外血管形成功能,最后将分化的内皮细胞体外种植于脱细胞基质血管表面构建组织工程血管?【结果】 基于KDR?vWF表达变化,间充质干细胞分化以第7天为界分为间充质干细胞分化血管祖细胞及血管祖细胞分化内皮细胞两期?早期活化ALK5(VFT组)?后期抑制ALK5 组(VFS组)其CD31+百分率分别为(9.65±2.75)%?(2.28±0.20)%,较标准组提高7.7倍(P = 0.006)?1.8倍(P = 0.013),差异具有统计学意义;诱导细胞具有体外成血管功能并可应用组织工程血管内膜层重建?【结论】 ALK5受体途径在骨髓间充质干细胞分化内皮细胞中呈阶段相关性:间充质干细胞分化血管祖细胞阶段活化ALK5促进内皮分化,血管祖细胞分化内皮细胞阶段则抑制ALK5促进内皮分化;提高内皮分化效率的细胞可应用组织工程血管内皮化?     

Toll样受体4信号通路分子与慢性心力衰竭严重程度和预后的关系分析

目的 探讨Toll样受体4(TLR-4)信号通路分子变化与慢性心力衰竭(CHF)严重程度和预后的关系。方法选择本院收治的117例CHF患者(病例组)和同期109例健康对照者(对照组),采用流式细胞仪检测其外周血单核细胞中TLR-4、核转录因子kappa B(NF-κB)和髓样分化因子(MyD88)的表达情况,分析它们与CHF的心功能分级、浆膜腔积液、再次入院和全因死亡的关系。结果病例组的外周血单核细胞的TLR-4、NF-κB和MyD88水平均显著高于对照组(均P<0.05);不同NYHA分级CHF患者的TLR-4(F=4.026,P=0.032)、NF-κB(F=5.152,P=0.025)和MyD88(F=7.323,P=0.019)水平具有显著差异;随访期间发生全因死亡患者的TLR-4(t=-2.149,P=0.033)和MyD88(t=-2.506,P=0.014)水平显著高于未死亡者;TLR-4作为预测发生全因死亡的灵敏度和特异度分别为83%和77%,而MyD88分别为77%和71%。结论TLR-4信号通路分子与CHF的心功能密切相关,TLR-4和MyD88是潜在的全因死亡预测分子。     

慢性疼痛患者发生抑郁和焦虑症状的研究

目的 探讨慢性疼痛患者疼痛与抑郁、焦虑间的关系.方法 选择2007年7月-2008年3月在首都医科大学宣武医院疼痛科住院的慢性疼痛患者131例.根据疼痛种类将患者分为3组,分别为三叉神经痛组(Ⅰ组)45例,颈腰椎源性疼痛组(Ⅱ组)39例,复杂神经痛组(Ⅲ组)47例.入院后均采用神经微创介入方法治疗疼痛.于治疗前、治疗后及治疗后3个月随访时采用疼痛视觉模拟评分(VAS)评定患者的疾病程度,使用汉密尔顿抑郁量表(24项HRSD)和汉密尔顿焦虑量表(HAMA)分别评定患者的抑郁和焦虑状况.结果 (1)治疗前Ⅰ组患者疼痛程度与Ⅱ组比较,治疗后Ⅰ组患者疼痛程度与Ⅲ组比较,治疗后3个月Ⅰ组患者疼痛程度与Ⅱ组、Ⅲ组比较,差异均有统计学意义(P＜0.05).各组治疗结束后及治疗后3个月的疼痛程度与治疗前比较,差异均有统计学意义(P＜0.05).(2)131例慢性疼痛住院患者中,抑郁和焦虑的发生率分别为49.62%和57.25%.治疗前Ⅲ组患者抑郁发生率(72.3%)与Ⅰ组(37.8%)、Ⅱ组(35.9%)比较,差异均有统计学意义(P＜0.01).Ⅰ、Ⅱ、Ⅲ组患者治疗结束后抑郁发生率(分别为4.4%、10.3%和25.5%)及治疗后3个月抑郁发生率(分别为0、15.2%和17.6%)与治疗前比较,差异均有统计学意义(P＜0.05).(3)治疗前Ⅲ组患者焦虑发生率(68.1%)与Ⅱ组(43.6%)比较,差异有统计学意义(P＜0.05).治疗前Ⅰ、Ⅱ、Ⅲ组患者焦虑发生率(分别为57.8%、43.6%和68.1%)与治疗结束后(分别为13.3%、15.4%和27.7%)及治疗后3个月(分别为0、24.2%和20.6%)比较,差异均有统计学意义(P＜0.05);Ⅰ组患者治疗结束后焦虑发生率与治疗后3个月比较,差异亦有统计学意义(P＜0.01).结论 慢性疼痛住院患者存在较高的抑郁和焦虑症状;三叉神经痛患者的疼痛程度最高,而复杂神经痛患者的抑郁、焦虑发生率最高;疼痛微创介入治疗后患者的疼痛程度及抑郁、焦虑发生率较治疗前显著下降.     

Xingshentongqiao Decoction Mediates Proliferation,Apoptosis, Orexin-A Receptor and Orexin-B Receptor Messenger Ribonucleic Acid Expression and Represses Mitogen-activated Protein Kinase Signaling

Background:Hypocretin (HCRT) signaling plays an important role in the pathogenesis of narcolepsy and can be significantly influenced by Chinese herbal therapy.Our previous study showed that xingshenton...     

N-甲基-D-天冬氨酸受体信号通路及其介导的细胞凋亡机制研究进展

N-甲基-D-天冬氨酸受体(NMDAR)是重要的离子型谷氨酸受体,具有配体及电压双重门控离子通道特性,组成及功能复杂,分布广泛,在多种疾病或应激状态的病理生理进程中起着关键作用。其可通过线粒体及内质网损伤、活性氧与过氧亚硝酸盐生成、丝裂原活化蛋白激酶及钙蛋白酶激活等不同途径介导细胞凋亡。本文就NMDAR的结构分布、生物特性及其介导的信号通路在细胞凋亡中作用机制等方面进行综述。     

Hedgehog通路介导上皮-间质转化促进CCl4诱导的大鼠肝纤维化进展

[目的]观察四氯化碳(carbon tetrachloride,CCl4)诱导大鼠肝纤维化发生发展过程中,Hedgehog信号通路及上皮-间质转化(epithelial-mesenchymal transition,EMT)关键分子的变化情况,探讨其可能的作用机制.[方法]将64只雄性无特殊病原体(specific p...     

Mangiferin Promotes Bregs Level,Activates Nrf2 Antioxidant Signaling,and Inhibits Proinflammatory Cytokine Expression in Murine Splenic Mononuclear Cells In Vitro

Recent studies indicated that regulatory B cells(Bregs)and nuclear factor erythroid 2-related factor 2(Nrf2)antioxidant signaling pathway play important roles i...     

栀子粗提物对抑郁模型小鼠行为学及海马神经发生的影响

目的观察栀子粗提物对慢性轻度应激模型小鼠行为学及海马神经发生的影响。方法采用10种不同应激源实施对小鼠连续10周刺激,从第3周开始口服给予栀子粗提物3个剂量治疗8周后,测定各组小鼠行为学改变,并采用NeuN和BrdU免疫组化观察海马区神经细胞的增殖情况。结果栀子粗提物高剂量组蔗糖饮水量明显增加（P〈0.05）,强迫游泳不动时间明显缩短（P〈0.05）;NeuN阳性表达升高（P〈0.01）,BrdU阳性细胞的面数密度亦显著增加（P〈0.05）。结论栀子粗提物对抑郁模型小鼠行为有明显改善作用,并能显著促进海马区神经元发生,提示栀子粗提物具有良好的抗抑郁作用。     

Rho A/Rho激酶信号通路参与慢性应激大鼠抑郁模型结肠动力的改变

目的:检测Rho A、Rock1、Rock2在抑郁大鼠结肠组织中mRNA及蛋白的表达,探讨Rho A/Rho激酶信号通路在抑郁大鼠结肠动力障碍中的可能机制.方法:通过慢性应激建立大鼠抑郁模型,正常组作对照,应用Real Time Q-PCR和Western blot检测Rho A、Rock1、Rock2在结肠组织中mRNA及蛋白的表达.结果:抑郁组结肠组织中的Rho A、Rock1、Rock2的mRNA及蛋白表达明显降低,与正常组比较差异有统计学意义(P＜0.01).结论:RhoA/Rho激酶信号通路在抑郁大鼠结肠动力障碍起着重要作用,但其作用机制仍需进一步的实验研究.     

Combination of Quercetin, Hirudin and Cinnamaldehyde Promotes Schwann Cell Differentiation and Myelination against High Glucose by Inhibiting ERK Signaling Pathway

Objective: To investigate the therapeutic and synergistic effects of QHC(combination of quercetin(Q), hirudin(H) and cinnamaldehyd(C)) on Schwann cell differentiation and myelination against high glucose(HG) induced injury. Methods: Primary-culture Schwann cells exposed to HG(50 mmol/L) for 72 h and Schwann cell–dorsal root ganglion(DRG) neuron cocultures exposed to HG(50 mmol/L) for 7 days were employed as in vitro model of diabetic neuropathy. The cells were randomly divided into 10 groups: control(CON, 25 mmol/L glucose), HG(50 mmol/L glucose), HG plus 10 μmol/L quercetin(Q), HG plus 0.04 IU/mL hirudin(H), HG plus 100 nmol/L cinnamaldehyd(C), HG plus 10 μmol/L quercetin and 0.04 IU/mL hirudin(QH), HG plus 10 μmol/L quercetin and 50 nmol/L cinnamaldehyd(QC), HG plus 0.04 IU/mL hirudin and 50 nmol/L cinnamaldehyd(HC), HG plus 10 μmol/L quercetin, 0.04 IU/mL hirudin and 50 nmol/L cinnamaldehyd(QHC) or 10 μmol/L U0126. Cell differentiation was evaluated by periaxin immunofluorescence staining. The protein expression levels of myelin protein zero(P0), myelin basic protein(MBP), myelin-associated glycoprotein(MAG), extracellular signal-regulated kinase(ERK), p-ERK, p-c-Jun, c-Jun, notch intracellular domain(NICD) and the mRNA expression levels of P0, MBP, MAG, Krox-20, Notch1 and Jagged1 were detected by Western blotting and real-time quantitative PCR analysis. The secretion of ciliary neurotrophic factor(CNTF) was determined by enzyme-linked immunosorbent assay(ELISA). The number and length of the myelin segments were evaluated by MBP immunofluorescence staining. The expression and the location of p-ERK in cocultures were detected by MAG and p-ERK immunofluorescence double staining. Results: Co-treatment with Q, C, H and their combination promoted Schwann cell differentiation, increased CNTF secretion, up-regulated the protein and m RNA expressions of myelin, and increased the number and length of the myelin segments(P0.01 or P0.05). In particular, the combination therapy of Q, H and C was superior to the respective monotherapy(P0.01). Combination therapy of QHC exhibited higher inhibitory activities for ERK signaling related molecules than each monomer or the combination of the two monomers(P0.01). Conclusions: QHC combination yielded synergy in promoting Schwann cell differentiation and myelination and the protective effect may involve in the inhibition of ERK signaling pathway, providing scientific evidence for better understanding of combination of Q, H and C in clinical applications.     

慢性肾小球肾炎患者血清抗α1受体和血管紧张素Ⅱ1受体自身抗体与肾损害程度的分析

目的探讨慢性肾小球肾炎（chronic glomerulonephritis,CGN）患者血清中抗血管紧张素Ⅱ1受体自身抗体（AT1受体抗体）和抗α1肾上腺受体自身抗体（α1受体抗体）产生的阳性率与血清肌酐水平的关系。方法以合成的AT1和α1受体多肽片段为抗原,应用酶联免疫吸附测定（ELISA）技术,检测111例慢性。肾小球肾炎患者（CGN）,61例高血压无肾损害患者,40例正常人血清中抗AT1和α1受体自身抗体。结果①CGN抗AT1和α1受体自身抗体阳性率分别为68．5％（76／111）和56．8％（63／111）明显高于单纯高血压组的34：4％（21／61）、27．9X（17／61）和正常对照组（分别为10．0％和12．5％）（P〈0．05,P〈0．01）;②CGN患者亚组比较,早期肾衰期抗AT1和α1受体自身抗体的检出阳性率最高,与晚期肾衰和尿毒症期比较具有显著性统计学意义（P〈0．01）;③血清肌酐水平比较分析（血清肌酐高于正常但〈450μmol／L组）抗AT1和抗α1受体自身抗体的检出阳性率,明显高于血清肌酐水平450～707μmol／L组和〉707μmol／L组,比较具有统计学意义（P〈0．01）。结论CGN发病与血清抗AT1和α1受体自身抗体产生有关,血清抗AT1和α1受体自身抗体与血清肌酐水平有关,免疫学机制可能参与CGN发病。     

隔物灸及情志护理治疗产后抑郁症的疗效观察及对体内雌、孕激素的影响

目的:研究隔物灸及情志护理治疗产后抑郁症的疗效,及对体内雌二醇、孕酮水平的影响。方法:根据随机的原则设立研究组和对照组,研究组给予隔物灸及情志护理,对照组给予盐酸舍曲林口服,50 mg,1次/d,治疗1个月,通过产后抑郁量表评价疗效,同时观察体内相应的性激素水平。结果:研究组痊愈22例、显效7例、有效4例、无效1例;对照组痊愈16例、显效9例、有效3例、无效6例。研究组治疗前血清雌二醇、孕酮为161.97±10.12、43.25±2.58,治疗后为229.48±7.01、19.45±3.94;对照组治疗前血清雌二醇、孕酮为159.01±8.45、44.46±3.39,治疗后为194.65±7.05、30.17±3.41。结论:在临床疗效上,研究组总有效率为97.06%,对照组总有效率为82.35%,明显优于对照组;2组均能升高患者雌二醇的水平,但是隔物灸及情志护理组升高的更明显,2组均能降低患者孕酮的水平,但是隔物灸及中医护理组降低的更明显;隔物灸及情志护理为临床治疗产后抑郁提供了新的治疗方法,值得进一步研究。     

老年患者慢性病负担对焦虑和抑郁的影响研究

背景　有研究表明慢性病与心理情绪密切相关,既往研究多集中在单个慢性病与焦虑、抑郁关系的研究,而缺乏对老年患者慢性病负担综合系统的研究。目的　探究综合性医院老年慢性病住院患者疾病负担与焦虑、抑郁的关系。方法　收集2018年3-6月于同济大学附属同济医院老年科住院的患者103例,运用Charlson合并症指数（CCI）来量化疾病负担,CCI评分≤3分为低疾病负担组,CCI评分>3分为高疾病负担组,采用广泛性焦虑量表（GAD-7）评估焦虑症状,健康问卷抑郁症状群量表（PHQ-9）评估抑郁症状,比较不同程度疾病负担的老年患者焦虑、抑郁的发生率。结果　103例老年患者GAD-7评分0~21分,平均（3.7±4.8）分,伴焦虑者28例（27.2%）;PHQ-9评分0~25分,平均（5.3±5.3）分,伴抑郁者42例（40.8%）,其中,合并焦虑及抑郁者22例（21.4%）。低疾病负担组54例（52.4%）,高疾病负担组49例（47.6%）。低疾病负担与高疾病负担的老年患者焦虑、抑郁发生率比较,差异无统计学意义（P>0.05）。不同性别、年龄亚组两组老年患者焦虑、抑郁发生率比较,差异均无统计学意义（P>0.05）。结论　老年住院患者焦虑、抑郁发生率较高,但未发现老年住院患者高、低疾病负担在焦虑、抑郁情绪间存在明显差异,可能负性情绪对合并多种慢性病的高龄老年人群影响较小。     

慢性阻塞性肺疾病合并抑郁的发生率及危险因素分析

目的了解慢性阻塞性肺疾病(COPD)患者合并抑郁的发生率,探讨COPD患者合并抑郁的危险因素。方法选择2011年1月至2013年1月兰州大学第二医院门诊和住院治疗的215例COPD稳定期患者,采用病人健康问卷抑郁量表(PHQ-9)对患者抑郁状况进行评价,同时完成CAT量表、肺功能检查及相关病史(性别、年龄、身高、体重、吸烟史、教育程度)的采集。根据患者的临床症状(mMRC或CAT量表)、未来急性加重的风险、肺功能的异常程度(FEV1%pred)以及并发症的情况进行综合评估而分成A、B、C、D组。采用2检验及多因素Logistic回归分析COPD患者合并抑郁的发生率及危险因素。结果 COPD患者合并抑郁的发生率为37.7%,COPD的A、B、C、D各组间的抑郁发生率分别为18.5%、35.8%、46.5%和62.5%,组间差异有统计学意义(P<0.01)。COPD合并抑郁的发生与患者的性别、年龄、教育程度、FEV1%pred、CAT、BMI有关,与年龄、FEV1%pred、BMI呈负相关,与教育程度、CAT评分呈正相关。而吸烟和FEV1/FVC与COPD合并抑郁无显著相关性(P>0.05)。结论 COPD患者容易合并抑郁,A、B、C、D各亚组之间抑郁的发生率有明显差异。COPD合并抑郁与性别、年龄、教育程度、FEV1%pred、BMI和CAT评分有关。