缺陷型和非缺陷型精神分裂症血清同型半胱氨酸及血脂研究

目的:研究缺陷型与非缺陷型精神分裂症患者同型半胱氨酸(Hcy)、血脂水平及其相关性。方法:于入院次日对58例住院缺陷型精神分裂症患者(DS)、60例非缺陷型精神分裂症患者(NDS)采用酶法检测血清Hcy、血脂水平,以阳性和阴性症状量表(PANSS)评估患者精神症状。采用同样方法检测64名对照者的Hcy、血脂水平,并比较三组间差异。结果:对照组Hcy、总胆固醇(TC)、高密度脂蛋白(HDL-C)水平均高于两患者组(P0.05),缺陷型与非缺陷型患者比较无统计学差异(P0.05);缺陷型PANSS阴性因子分高于非缺陷型(t=24.840,P0.001),非缺陷型PANSS阳性因子分高于缺陷型(t=29.918,P0.001),PANSS总分(t=0.275,P=0.784)、PANSS一般精神病理分(t=1.005,P=0.317)两组比较差异无统计学意义;三组Hcy水平均与性别相关,即男性高于女性,缺陷型(t=3.146,P=0.003),非缺陷型(t=2.624,P=0.011),对照组(t=4.753,P0.001);缺陷型、非缺陷型患者HDLC女性均高于男性(t=2.711,P=0.009;t=3.220,P=0.002);对照组血脂各项指标男女无统计学差异(P0.05)。结论:在青壮年,精神分裂症患者Hcy和血脂水平并没有高于正常人群;缺陷型与非缺陷型患者Hcy和血脂水平无差异,但男性患者Hcy高于女性,而女性HDL-C高于男性,且缺陷型患者Hcy与阴性症状相关。     

酸性神经酰胺酶基因与精神分裂症症状数量性状的关联研究

目的 探讨酸性神经酰胺酶基因(ASAH1)与精神分裂症症状数量性状的关联.方法 应用聚合酶链反应及限制性片段长度多态性技术,对254例精神分裂症患者ASAH1基因的3个单核苷酸多态性(rs3753118、rs3753116及rs7830490)进行检测;使用阳性和阴性症状量表(PANSS)评定患者疾病表型的数量性状.结果 (1)患者rs3753118位点3种基因型间的阳性症状分的差异有统计学意义(F=3.506,P＜0.05);rs3753116位点3种基因型间的PANSS总分及阴性症状分的差异均有统计学意义(F=3.548,P＜0.05;F=3.358,P＜0.05).经两两比较,rs3753118位点C/C基因型组患者的阳性症状分及一般精神病理分明显高于C/T基因型组患者;rs3753116位点G/G基因型组患者的PANSS总分及阴性症状分明显高于A/G基因型组患者,且G/G基因型组患者的阴性症状分明显高于A/A基因型组患者,差异均有统计学意义(P均＜0.05).(2)患者3个位点各等位基因间的PANSS量表评分的差异无统计学意义(P＞0.05).(3)患者rs3753118C-rs3753116G单体型者及rs3753118C-rs3753116G-rs7830490A单体型者,其PANSS总分及阴性症状分均明显高于参照单体型者,差异均有统计学意义(P均＜0.05).结论 ASAH1基因区域可能存在精神分裂症症状数量性状位点.     

首发精神分裂症患者的脑灰质减少

目的 采用基于体素的形态学(VBM)分析方法对高分辨磁共振图像进行分析,研究首发精神分裂症患者大脑灰质变化,探讨患者脑灰质改变与临床症状之间的关系.方法 对符合CCMD-3诊断标准的首发精神分裂症患者以及健康志愿者各16例进行脑结构核磁共振扫描,并应用VBM进行脑灰质体积分析.所有患者均完成阳性与阴性症状量表(PANSS)评估.结果 与健康对照相比,患者组灰质密度降低的脑区有右侧小脑(t=5.17,P＜0.001)、右侧顶上回(t=5.01,P＜0.001)、左侧颞上回至岛叶被盖(t=4.79,P＜0.001)、左侧额中回(t=4.71,P＜ 0.001)、左侧额下回(t=4.70,P＜0.001)、右侧舌回(t=4.62,P＜ 0.001)、左侧海马杏仁体(t=4.11,P＜0.001).患者组左侧Heschl's回的灰质密度与PANSS量表总分(r=-0.509,P=0.044)以及PANSS阳性症状量表得分(r=-0.554,P=0.026)呈显著负相关.结论 首发精神分裂症患者的脑灰质减少以左侧额、颞叶为主,其中左侧Heschl's回灰质变化与患者的精神病性症状有相关性.     

低频重复经颅磁刺激对精神分裂症患者血清BDNF水平影响的对照研究

目的 初步探讨低频重复经颅磁刺激(Repetitive transcranial magnetic stimulation,rTMS)治疗对精神分裂症患者血清脑源性神经营养因子(Brain-derived neurotrophic factor,BDNF)的影响,以及血清BDNF变化与疗效的相关性.方法 100例伴有幻听症状的精神分裂症患者按1∶1∶1∶1比率随机分为A、B、C、D四组,其中A、C组为典型抗精神病药物治疗;B、D组为非典型抗精神病药物治疗;C、D组合并rTMS治疗.25例正常人作为正常对照组(E组).真性治疗组给予6周共20次低频(1Hz)rTMS治疗.采用酶联夹心免疫吸附法测定基线、治疗2周、治疗6周的血清BDNF浓度.使用阳性和阴性症状量表(Positive and negative syndrome scale,PANSS)、临床疗效总评量表(Clinical Global Impression,CGI)评估病情严重程度及疗效.以皮尔森相关分析(Pearson correlation)方法来分析血清BDNF水平与疗效之间的相关性.结果 与治疗前相比,治疗10次后和20次后D组患者BDNF极显著升高(P＜0.001);B、C组治疗后BDNF显著升高(P＜0.05);A组治疗前后无显著性差异.D组治疗20次后极显著高于A、B两组(P＜0.01).入组治疗时BDNF与治疗结束时CGI-S评分、CGI-GI评分负相关(r=-0.345,P＜0.001;r=-0.217,P＜0.05),与治疗前、后PANSS总分负相关(r=-0.202,P＜0.05;r=-0.532,P＜0.001).结论 低频rTMS治疗能提高精神分裂症血清BDNF浓度,可能有预测疗效的作用.     

首发未服药精神分裂症患者血清S100B蛋白浓度变化

目的 探讨血清S100B蛋白浓度与首发未服用抗精神病药的精神分裂症患者精神病理症状间的关系.方法 采用酶联免疫(ELISA)方法 检测64例首发未服用抗精神病药精神分裂症患者和66名正常对照的血清S100B蛋白浓度,比较2组间的差异;采用阳性和阴性症状量表(PANSS)评定精神病理症状,分析血清S100B蛋白浓度与PANSS评分、患者年龄、发病年龄、病程间的关系.结果 ①患者组血清S100B浓度明显高于对照组,筹异有统计学意义[(0.27±0.13)μg/L vs(0.11±0.04)μg/L,t=10.89,P＜0.001];②患者组中偏执型、瓦解型、未分化型、残留型4个亚组间血清S100B浓度的差异有统计学意义(F=4.63,P=0.006),残留型组明显高于偏执型组(P=0.001)、瓦解型组(P=0.012);且各亚型组均明显高于对照组(P＜0.001).③患者组血清S100B浓度与年龄、总病程、PANSS总分及其阴性症状因子分相关(r为0.36、0.46、0.42、-0.38,P均小于0.005).结论 首发未服药的精神分裂症患者血清S100B浓度升高,并与某些病理症状尤其是阴性症状关联,在一定程度上可反映疾病严重程度.     

奎硫平单用与合并阿立哌唑对精神分裂症患者体质量的影响

目的:探讨奎硫平与阿立哌唑合用及单用奎硫平对精神分裂症患者体质量、腹围及体质量指数(BMI)的影响. 方法:将63例精神分裂症患者随机分为阿立哌唑合并奎硫平组31例(研究组)及单用奎硫平组32例(对照组).在治疗前及治疗6周,用阳性和阴性症状量表(PANSS)评定疗效,并进行体质量、腹围及BMI的测定. 结果:治疗6周两组PANSS评分差异无统计学意义(t=1.35,P＞0.05);研究组治疗后腹围值增加明显(t=7.76,P＜0.05),对照组体质量、腹围及BMI值均增加明显(P＜0.05);组间变化值的比较体质量、腹围及BMI增加值均较对照组小(P＜0.05). 结论:合用阿立哌唑能够明显减轻奎硫平对精神分裂症患者体质量增加的影响     

首发精神分裂症人面孔彩照诱发关联性负变的初步研究

目的 研究熟悉人和陌生人面孔彩色照片与短声组成不同的刺激序列诱发关联性负变(CNV)在精神分裂症中的应用.方法 应用中国广州三甲J-1脑电生理仪,检测30例首发精神分裂症患者和29名正常对照的CNV,进行横断面的病例对照研究.结果 精神分裂症组波形不规则.对照组A点潜伏期为(320±57)ms,精神分裂症组为(373±61)ms,精神分裂症患者CNV潜伏期A点延迟(t=4.59,P＝0.007),对照组波幅B(16±5)μV,精神分裂症组为(9±6)μV,精神分裂症患者波幅B降低(t=4.51,P＝0.008 ).结论 首发精神分裂症患者面孔照片诱发CNV A点潜伏期延迟,波幅B降低,CNV变化有待进一步探讨.     

首次发病的青少年精神分裂症患者执行功能的研究

目的:探讨首次发病的青少年精神分裂症患者执行功能及其与精神症状的关系. 方法:采用威斯康星卡片分类测验(WCST)及韦克斯勒记忆量表第3版(WMS-Ⅲ)空间广度测验测试75例首次发病的青少年精神分裂症患者(病例组)和80名健康对照者(对照组)的执行功能;病例组同时应用阳性和阴性症状量表(PANSS)评定病情. 结果:病例组WCST的错误总数、持续反应数和持续错误数显著高于对照组,正确总数显著低于对照组(P均＜0.01);WMS-Ⅲ总分和空间广度逆行分显著低于对照组(P均＜0.05).病例组PANSS阴性症状分与WMS-Ⅲ空间广度逆行分及总分负相关(r=-0.276,r=-0.230;P均＜0.05);阳性症状分与WCST完成分类数负相关(r=-0.258,P＜0.05);一般病理学总分与WMS-Ⅲ空间广度逆行分负相关(r=-0.244,P＜0.05). 结论:首次发病的青少年精神分裂症患者执行功能显著受损,并与病情有关.     

精神分裂症患者自我面孔识别能力与自我接纳、自我效能及自尊的相关性

目的:探讨精神分裂症患者自我面孔识别能力及其与自我接纳、自我效能及自尊的关系.方法:采用自我面孔识别任务(SFRT)对62例精神分裂症患者(患者组)进行测试,并与54名健康者(正常对照组)作比较,同时采用自我接纳问卷(SAQ)、一般自我效能感量表(GSES)和罗森伯格自尊量表(SES)作评估. 结果:患者组SFRT平均反应时(2189±1138) ms明显长于对照组(1152±326)ms(Z=-6.86,P＜0.001),正确率(81±16)％低于对照组(88±6)％(Z=-2.82,P＜0.01).患者组SAQ评分平均(38.37±7.25)分低于对照组(43.19±5.61)分(Z=-3.42,P＜0.01);SES评分平均(21.21±5.22)分低于对照组(23.33±4.44)分(Z=-2.13,P＜0.05);GSES评分平均(22.27±5.98)分低于对照组(24.41 ±4.83)分(Z=-2.29,P＜0.05).相关分析显示,患者组SFRT平均反应时与SES得分(r=-0.430)、GSES得分(r=-0.396)均呈负相关(P均＜0.01);SFRT正确率与SAQ总分(r=0.367)、自我接纳因子分(r=0.298)、自我评价因子分(r=0.266)均呈正相关(P＜0.05或P＜0.01).结论:精神分裂症患者存在自我面孔识别能力的缺损,自我接纳、自尊水平及自我效能均低于正常人.     

精神分裂症患者情绪记忆损害的研究

目的 探讨精神分裂症患者的情绪记忆及其与精神症状的相关性.方法 采用情绪图片的同忆和再认测试评定40例精神分裂症患者与40名止常对照的情绪记忆,同时采用阳性与阴性症状量表(PANSS)评定患者临床症状.结果 两组间图片评分测试结束10 min后和72 h后对负性和中性图片的回忆率以及负性和止性图片的再认正确率差异均有统计学意义(P＜0.05).PANSS量衷阴性症状评分与负性和正性图片再认正确率呈负相关(r=-0.91,P＜0.01;r=-0.38,P＜0.05).患者组病程与10 min后负性图片回忆率(r=-0.33,P＜0.05)、72h后负性和正性图片回忆率(r=-0.36,P＜0.05;r=-0.36,P＜0.05)、负性图片再认正确率(r=-0.34,P＜0.05)呈负相关.结论 精神分裂症患者存在情绪记忆损害,且与精神症状相关.     

Environmental factors in the development and progression of late-onset Alzheimer＇s disease

Late-onset Alzheimer＇s disease （LOAD） is an age-related neurodegenerative disorder characterized by gradual loss of synapses and neurons, but its pathogenesis remains to be clarified. Neurons live in an environment constituted by neurons themselves and glial cells. In this review, we propose that the neuronal degeneration in the AD brain is partially caused by diverse environmental factors. We first discuss various environmental stresses and the corresponding responses at different levels. Then we propose some mechanisms underlying the specific pathological changes, in particular, hypothalamic-pituitary adrenal axis dysfunction at the systemic level; cerebrovascular dysfunction, metal toxicity, glial activation, and Aβ toxicity at the intercellular level; and kinase-phosphatase imbalance and epigenetic modification at the intracellular level. Finally, we discuss the possibility of developing new strategies for the prevention and treatment of LOAD from the perspective of environmental stress. We conclude that environmental factors play a significant role in the development of LOAD through multiple pathological mechanisms.     

高血压脑出血的显微外科治疗进展

高血压脑出血（Hypertensive intrac-rebral hemorrhage,HICH）是具有高发病率、高病死率、高致残率的急性脑血管疾病,占所有脑卒中患者的10%-20%,早期病死率可高达49.4%。随着人口老龄化,其发病率逐年提高;而外科手术的干预,使其病死率有所下降,但致残率居高不下。如何提高手术疗效和患者生存质量,一直是神经外科医师努力的方向。微侵袭血肿清除术因其手术创伤小,恢复快,是目前国内治疗高血压脑出血的重要手段。     

神经内镜联合亚低温治疗高血压基底节区脑出血

目的 探讨神经内镜联合亚低温在治疗高血压基底节区脑出血中的临床应用价值.方法 回顾性分析我院神经内镜治疗高血压基底节区脑出血患者40例的临床资料,并对治疗结果进行分析.结果 神经内镜治疗组22例(甲组),神经内镜联合亚低温治疗组18例(乙组),术后3个月根据GCS评分,甲组恢复良好1例,中残4例,重残6例,植物生存6例,死亡5例;乙组恢复良好4例,中残8例,重残3例,植物生存1例,死亡2例,两组比较差异有统计学意义(P＜0.05).两组颅内压比较第1天两者差异不明显,但第2、3天亚低温组颅内压明显降低.结论 神经内镜是治疗高血压基底节区脑出血较为有效的手术方式,联合亚低温治疗能有效降低颅内压,改善术后神经功能恢复,具有较好的临床应用价值.     

Total saponins of Panax ginseng effects on proliferation and differentiation of human embryonic neural stem cells and in a Parkinson’s disease mouse model

BACKGROUND： Total saponins of Panax ginseng （TSPG） exhibits neuroprotection against Parkinson＇s disease in the substantia nigra. OBJECTIVE： To investigate the effects of TSPG on human embryonic neural stem cells （NSCs） proliferation and differentiation into dopaminergic neurons using in vitro studies, and to observe NSC differentiation in a mouse model of Parkinson＇s disease, as well as behavioral changes before and after transplantation. DESIGN, TIME AND SETTING： In vitro neural cell biology trial and in vivo randomized, controlled animal trial were performed at the Institute of Basic Medical Sciences, Chongqing Medical University between September 2004 and December 2007. MATERIALS： TSPG （purity 〉 95%） was isolated, extracted, and identified by Chongqing Academy of Chinese Materia Medica. Recombinant human basic fibroblast growth factor （bFGF） and recombinant human epidermal growth factor （EGF） were purchased from PeproTech, USA. A total of 25 C57/BL6J mice, aged 18-20 weeks were included. Twenty were used to establish a Parkinson＇s disease model with i.p. injection of MPTP （1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine） and TSPG alone or combined with interleukin-1 （IL-1）-treated NSCs prior to transplantation into the corpus striatum. The remaining five mice were pretreated for 3 days with TSPG prior to MPTP injection, serving as the TSPG prevention group. METHODS： Primary NSCs were isolated, cultured and purified from embryonic cerebral cortex. Immunocytochemistry was employed to detect specific antigen expression in the NSCs. In vitro experiment： （1） to induce proliferation, NSCs were treated with TSPG, EGF＋bFGF, or TSPG＋EGF＋bFGF, respectively; （2） to induce dopaminergic neuronal differentiation, NSCs were treated with TSPG, IL-1, or TSPG＋IL-1, respectively. MAIN OUTCOME MEASURES： In vitro experiment： the effects of TSPG on NSCs proliferation were evaluated with flow cytometry and MTT assay. Tyrosine hydroxylase expression was determined by immunocytochemistry assay to observe effects of TSPG on dopaminergic neuronal differentiation. In vivo experiment： differentiation of grafted NSCs in the mouse brain was determined by immunohistochemical staining. Behavioral changes were evaluated by spontaneous activity frequency, memory function, and score of paralysis agitans. RESULTS： （1） NSCs were cultured and passaged for more than three passages. Immunocytochemistry revealed positive nestin staining, as well as neurofilament protein and glial fibrillary acidic protein. （2） TSPG significantly increased NSC proliferation, in particular when combined with EGF and bFGF, which was twice as effective as FGF or bFGF alone. TSPG also induced dopaminergic differentiation in NSCs, in particular when TSPG was added together with IL-1, resulting in an effect five times greater than that of IL-1 alone. （3） At day 30 following transplantation, most NSCs in the TSPG prevention group differentiated into dopaminergic neurons, and the scores of paralysis agitans, spontaneous activity, and memory function were significantly increased compared with TSPG alone or TSPG＋IL-1 groups （P 〈 0.05）. CONCLUSION： TSPG stimulated NSC proliferation, in particular when combined with FGF and bFGF. TSPG significantly induced dopaminergic neuronal differentiation of NSCs, and the effect was greater when combined with IL-1. In addition, TSPG greatly improved behavior in the Parkinson＇s disease mouse model following NSC transplantation. Following NSC transplantation, TSPG pretreatment exhibited superior efficacy over either TSPG alone or TSPG in combination with IL-1, in terms of behavioral improvements in the Parkinson＇s disease mouse model.     

Effects of p75 neurotrophin receptor knockout on axonal regeneration in a mouse model of facial nerve injury

BACKGROUND： Previous studies have shown that p75 neurotrophin receptor plays an important role in peripheral nerve injury. However, the role of p75 neurotrophin receptor in the regeneration of peripheral nerves remains poorly understood. OBJECTIVE： To study the effect of p75 neurotrophin receptor on facial nerve regeneration. DESIGN, TIME AND SETTING： A randomized controlled experiment was performed in the Regeneration Laboratory of Flinders University, Australia and the Biomedical Laboratory of Dentistry School, Shandong University from March 2005 to February 2006. MATERIALS： Cholera toxin B subunit, fast blue, and biotin rabbit-anti goat IgG were provided by Sigma, USA; goat-anti choleratoxin B subunit ant/body was provided by List Biologicals, USA. METHODS： In p75 neurotrophin receptor knockout and wild type 129/sv mice, the facial nerves on one side were crushed. At days 2 and 4 following injury, regenerating motor neurons in the facial nuclei were labeled by fast blue, and the regenerating axon was labeled by the anterograde tracer choleratoxin B subunit. MAIN OUTCOME MEASURES： Axonal regenerative velocity and number were detected by immunohistochemical staining of choleratoxin B subunit, growth-associated protein, protein gene product 9.5, and calcitonin-gene-related peptide; survival of motor neurons in the facial nuclei was detected by retrograde fast blue. RESULTS： Axonal growth in the facial nerve of p75 neurotrophin receptor knockout mice was significantly less than in wild type mice. At day 7 after injury, the number of regenerating motor neurons in p75 neurotrophin receptor knockout mice remained significantly less than in wild type mice （P 〈 0.05）. The number of positively stained fibers for growth-associated protein-43, protein gene product 9.5, and calcitonin-gene-related peptide in p75 neurotrophin receptor knockout mice was significantly less than in wild type mice （P 〈 0.01）. CONCLUSION： p75 neurotrophin receptor promoted axonal regeneration and enhanced the survival rate of motor neurons following facial nerve injury.     

Disrupted structural and functional brain connectomes in mild cognitive impairment and Alzheimer＇s disease

Alzheimer＇s disease （AD） is the most common type of dementia, comprising an estimated 60-80% of all dementia cases. It is clinically characterized by impairments of memory and other cognitive functions. Previous studies have demonstrated that these impairments are associated with abnormal structural and functional connections among brain regions, leading to a disconnection concept of AD. With the advent of a combination of non-invasive neuroimaging （structural magnetic resonance imaging （MRI）, diffusion MRI, and functional MRI） and neurophysiological techniques （electroencephalography and magnetoencephaJography） with graph theoretical analysis, recent studies have shown that patients with AD and mild cognitive impairment （MCI）, the prodromal stage of AD, exhibit disrupted topological organization in large-scale brain networks （i.e., connectomics） and that this disruption is significantly correlated with the decline of cognitive functions. In this review, we summarize the recent progress of brain connectomics in AD and MCI, focusing on the changes in the topological organization of large-scale structural and functional brain networks using graph theoretical approaches. Based on the two different perspectives of information segregation and integration, the literature reviewed here suggests that AD and MCI are associated with disrupted segregation and integration in brain networks. Thus, these connectomics studies open up a new window for understanding the pathophysiological mechanisms of AD and demonstrate the potential to uncover imaging biomarkers for clinical diagnosis and treatment evaluation for this disease.     

Edema and neuronal apoptosis in the hippocampus and cortex of elderly rats following transient cerebral ischemia/reperfusion injury

BACKGROUND： Previous studies of cerebral ischemia have used young animals, with an ischemic time greater than 5 minutes （safe time limit）. Despite an increased understanding of neuronal apoptosis, it remains uncertain whether brief cerebral ischemic events of 5 minutes or less damage brain tissue in elderly rodents. OBJECTIVE： To investigate the effects of transient cerebral ischemia （5 minutes）/reperfusion injury on brain cortical and hippocampal edema, aquaporin-4 （AQP-4） expression, and neuronal apoptosis in aged rats, and to compare ischemic sensitivity between cortex and hippocampus. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Institute of Cerebrovascular Disease, Qingdao University Medical School from April 2008 to March 2009. MATERIALS： Rabbit anti-AQP-4 polyclonal antibody, TUNEL kit, and SABC immunohistochemistry kit were purchased from Wuhan Boster Bioengineering, China. METHODS： A total of 160 healthy, male, aged 19-21 months, Wistar rats were randomly assigned to 4 groups： sham-surgery, and ischemia 1-, 3-, and 5-minute groups, with 40 rats in each group. The global cerebral ischemia model was established using the Pusinelli four-vessel occlusion, and the three cerebral ischemia groups were subdivided into reperfusion 12-hour, 1-, 2-, 3-, and 7-day subgroups, with 8 rats in each subgroup. The sham-surgery group was subjected to exposure of the first cervical bilateral alar foramina and bilateral common carotid arteries. MAIN OUTCOME MEASURES： The dry-wet weight assay was used to measure brain water content and histopathology of the cortex and hippocampus was observed following hematoxylin-eosin staining. In addition, cortical and hippocampal AQP-4 expression was detected by streptavidin-biotin complex immunohistochemistry, and neuronal apoptosis was detected by the TUNEL method. RESULTS： There was no significant difference in brain water content or AQP-4 expression in the cortex and hippocampus between ischemia 1- and 3-minute groups and the sham-surgery group or brain water content or AQP-4 expression in the cortex between ischemia 5-minute group and sham-surgery group （P 〉 0.05）. However, brain water content and AQP-4 expression in the hippocampus after 5 minutes of cerebral ischemia were significantly increased compared with the sham-surgery group （P 〈 0.05 or P 〈 0.01）. Several TUNEL-positive cells were observed in the cortex and hippocampus of the sham-surgery group and ischemia 1-minute group, as well as in the cortex of the ischemia 3-minute group. In addition, the number of apoptotic neurons in the hippocampus of ischemia 3-minute group and in the cortex and hippocampus of ischemia 5-minute group was significantly increased （P 〈 0.05 or P 〈 0.01 ）. Neuronal apoptosis was increased after 12 hours of ischemia/reperfusion, and it reached a peak by 2 days （P 〈 0.01）. CONCLUSION： Transient cerebral ischemia （5 minutes） resulted in increased hippocampal edema, AQP-4 expression, and neuronal apoptosis. Moreover, cerebral ischemia had a greater effect on neuronal apoptosis than brain edema or AQP-4 expression, and the hippocampus was more sensitive than the cortex.     

在SK-N-SH细胞中抑制干预β-淀粉样前体蛋白裂解酶基因和淀粉样β前体蛋白基因

BACKGROUND： Previous studies have demonstrated that Piper futokadsura stem selectively inhibits expression of amyloid precursor protein （APP） at the mRNA level. In addition, the piperlonguminine （A） and dihydropiperlonguminine （B） components （1 ： 0.8）, which can be separated from Futokadsura stem, selectively inhibit expression of the APP at mRNA and protein levels. OBJECTIVE： Based on previous findings, the present study investigated the effects of β-site amyloid precursor protein cleaving enzyme （BACE1） and APP genes on the production of β-amyloid peptide 42 （Aβ42） in human neuroblastoma cells （SK-N-SH cells） using small interfering RNAs （siRNAs） and A/B components separated from Futokadsura stem, respectively. DESIGN, TIME AND SETTING： A gene interference-based randomized, controlled, in vitro experiment was performed at the Key Laboratory of Cardiovascular Remodeling and Function Research, Ministries of Education and Public Health, and Institute of Pharmacologic Research, School of Pharmaceutical Science ＆ Department of Biochemistry, School of Medicine, Shandong University between July 2006 and December 2007. MATERIALS： SK-N-SH cells were provided by Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China; mouse anti-human BACE1 monoclonal antibody was purchased from R＆D Systems, USA; mouse anti-human APP monoclonal antibody was purchased from Cell Signaling Technology, USA; and horseradish peroxidase （HRP）-conjugated goat anti-mouse IgG was provided by Sigma, USA. METHODS： The human BACE1 cDNA sequence was obtained from NCBI website （www.ncbi.nlm.nih.gov/sites/entrez）. Three pairs of siRNAs, specific to human BACE1 gene, were synthesized through the use of Silencer pre-designed siRNA specification, and were transfected into SK-N-SH cells with siPORT NeoFX transfection agent to compare the effects of different concentrations of siRNAs （10-50 nmol/L） on SK-N-SH cells. Futokadsura stem was separated and purified with chemical methods, and the crystal was composed of A/B components, with an A to B ratio of 1：0.8. The A/B （1 ： 0.8） components were added to the SK-N-SH cells at different concentrations （13.13, 6.56, and 3.28 mg/mL）. MAIN OUTCOME MEASURES： Using RT-PCR and Western blot methods, BACE1 and APP expression at mRNA and protein levels was detected in SK-N-SH cells following treatment with different siRNAs and concentrations of Futokadsura stem-separated A/B components, respectively. Altered Aβ42 secretion by SK-N-SH cells was determined by ELISA. RESULTS： BACE1 mRNA and protein levels were significantly suppressed by 40 and 50 nmol/L siRNAs at 48 hours post-transfection. A/B components （1 ： 0.8）, which were separated from Futokadsura stem, selectively inhibited mRNA and protein expression of APP in SK-N-SH cells. Aβ42 secretion by SK-N-SH cells was significantly decreased following treatment with siRNAs or A/B components. CONCLUSION： Inhibition of BACE1 and APP genes by various materials and methods efficiently decreased production of Aβ42.     

墨蝶呤还原酶基因与精神分裂症相关性的研究进展

墨蝶呤还原酶（SPR）催化四氢生物蝶呤（BH4）从头合成途径的最后一步反应。SPR基因遗传缺陷或突变可导致BH。的合成紊乱,影响单胺类神经递质（如多巴胺、5-羟色胺及谷氨酸等）的合成或释放,进而参与包括精神分裂症在内的多种神经精神系统疾病的发生发展过程。此外,SPR基因敲除小鼠表现出持续增强的自主活动等类精神分裂症症状,说明该基因在精神分裂症的发病中扮演重要的角色。进一步研究SPR基因及其单核苷酸多态性的功能,可为阐明精神分裂症的发病机制提供重要的线索,也为新一代抗精神病药物的研制及开发开拓新的视野。现对SPR基因与精神分裂症的相关研究做一综述。