高血压患者颈动脉斑块和急性缺血性脑卒中的相关性研究

目的探讨高血压患者颈动脉斑块和急性缺血性脑卒中的相关性,以减少其发生率。方法对2013-06—2014-06收治入院的177例高血压患者的临床资料进行回顾性分析,其中发生急性缺血性脑卒中的81例为观察组,未发生急性缺血性脑卒中的96例为对照组,分析2组患者颈动脉斑块类型及发生率,采用Logistic逐步回归分析,分析颈动脉斑块的发生与急性缺血性脑卒中的相关性。结果 2组患者颈动脉斑块发生率分别为76.54%和43.75%,观察组高于对照组,差异有统计学意义(P0.05);多因素回归分析表明,颈动脉斑块的发生增加急性缺血性脑卒中风险(OR=5.867,P=0.001)。结论合并急性缺血性脑卒中的高血压患者发生颈动脉斑块的几率高于未发生急性缺血性脑卒中的高血压患者,颈动脉斑块形成是高血压患者发生急性缺血性脑卒中的独立危险因素。     

急性轻型脑梗死及短暂性脑缺血患者认知障碍的危险因素分析

目的探讨急性轻型缺血性脑卒中(NIHSS评分5分)及短暂性脑缺血患者认知功能障碍的危险因素。方法纳入急性轻型缺血性卒中及TIA患者93人,收集患者的血液学检查、头部MRI、颈动脉超声等临床资料,入院后3 d内采用简易精神状态评估量表(MMSE)评分评估患者的认知功能,分为认知功能障碍组及非障碍组,对两组的临床资料进行统计学分析。结果 45. 1%的轻型缺血性卒中合并认知障碍,认知障碍与认知正常两组间单因素分析表明患者的受教育水平、年龄、既往静息性腔梗、超敏C-反应蛋白(HS-CRP)增高是急性轻型脑梗死及TIA后认知功能障碍的独立危险因素(P 0. 05),相关分析表明HS-CRP水平与MMSE评分无线性相关(P0. 05)。结论 HS-CRP增高及既往静息性腔梗是急性轻型缺血性脑卒中和TIA后认知功能障碍的独立危险因素。     

伴B-FABP增高的缺血性卒中相关危险因素分析

目的探讨伴脑型脂肪酸结合蛋白(B-FABP)增高的缺血性卒中患者的相关危险因素。方法以2015-09—2016-09我院收治的54例伴B-FABP增高的缺血性脑卒中患者为研究组,以同期收治的非B-FABP增高的缺血性脑卒中患者54例为对照组。对比2组一般资料,并对研究组患者的相关危险因素进行分析。结果性别(男)、冠心病、高血压、饮酒、吸烟、糖尿病、甘油三酯、总胆固醇、高密度脂蛋白、低密度脂蛋白等为伴B-FABP增高的缺血性脑卒中患者的相关危险因素(P0.05),且性别(男)、冠心病、高血压、饮酒、吸烟、糖尿病、甘油三酯、总胆固醇、低密度脂蛋白与缺血性脑卒中患者B-FABP增高呈正相关(P0.05),而高密度脂蛋白与B-FABP增高呈负相关(P0.05);Logistic多因素回归分析显示,缺血性脑卒中患者B-FABP增高的独立危险因素为高血压及糖尿病,保护因素为高密度脂蛋白。结论影响缺血性脑卒中患者B-FABP水平的主要危险因素为高血压、糖尿病、高密度脂蛋白。临床需采取积极措施,加强对高危人群相关危险因素的监测,并尽早采取积极措施进行干预,从而最大限度减少缺血性脑卒中。     

进展性大动脉粥样硬化型脑梗死的危险因素分析

目的探讨中国缺血性脑卒中亚型(CISS)分型中大动脉粥样硬化型(LAA)脑梗死病情进展的危险因素。方法前瞻性收集急性LAA脑梗死患者,根据美国国立卫生研究院卒中量表(NIHSS评分)评估患者病情是否进展,对可能影响患者病情进展的因素进行统计分析。结果共纳入351例患者,其中进展组112例(31.91%),非进展组239例(68.09%)。单因素分析2组患者高血压病史、饮酒史、空腹血糖、白细胞总数、纤维蛋白原水平、入院时收缩压及舒张压、入院时NIHSS评分、颅内外血管重度狭窄/闭塞、肺部感染、泌尿系感染、电解质紊乱有明显差异(P0.1),多因素Logistic逐步回归分析显示入院时收缩压、白细胞总数、颅内外血管重度狭窄/闭塞、纤维蛋白原水平、肺部感染、相较于轻度神经功能缺损的中度及重度神经功能缺损是进展性LAA脑梗死的独立危险因素。结论入院收缩压增高、白细胞总数增高、颅内外血管重度狭窄/闭塞、纤维蛋白原水平增高、肺部感染、中度及重度神经功能缺损是进展性LAA脑梗死的独立危险因素。     

缺血性脑卒中患者发病1年后的生存情况分析

目的探讨缺血性脑卒中患者发病1年后的生存情况。方法对116例缺血性脑卒中患者进行临床资料采集并随访1年,对患者随访1年后的存活情况进行统计,并分析患者发病1年内病死的危险因素。结果本组患者随访1年后死亡21例,病死率为18.1%。与存活患者比较,死亡患者的年龄明显增高,肺部感染的比例明显增高(均P0.05)。COX回归分析显示,高龄和肺部感染为缺血性脑卒患者发病1年内病死的独立危险因素(r=1.058,95%CI:1.010~1.108,P=0.018;r=0.119,95%CI:0.037~0.375,P=0.000)。结论缺血性脑卒中患者发病1年后病死率为18.1%。高龄和肺部感染的缺血性脑卒中患者发病1年内病死的风险较高。     

尿微量白蛋白/尿肌酐比率与急性缺血性脑卒中早期神经功能恶化的相关性分析

目的探讨尿微量白蛋白/尿肌酐比率(UACR)和急性缺血性脑卒中患者发生早期神经功能恶化(END)的关系。方法收集2014年07月至2016月12月于南京医科大学第一附属医院老年医学科、神经内科住院,且头颅MRI和MRA确诊为急性缺血性脑卒中患者216名的临床资料。入院7 d内依据NIHSS多次对患者神经功能缺损症状进行评估,任意1次评分较入院分值增加≥2分定义为END,并将研究对象分为END组和非END组。通过比较两组间各因素差异分析、构建Logistics回归模型和分层分析研究UACR水平和END的相关性。结果与非END组相比,END组饮酒比例、NIHSS评分和UACR水平均显著增高,差异具有统计学意义(均P0.05)。Logistic回归结果显示,UACR水平是急性缺血性脑卒中患者发生END的独立危险因素(OR=4.54,95%CI:2.08~9.94,P0.001)。分层分析证实较高的UACR水平在年龄67岁、入院时NIHSS评分3分、合并高血压、TOAST分型大动脉粥样硬化型、男性患者中与发生END独立相关。结论尿微量白蛋白/尿肌酐比率升高是急性缺血性脑卒中发生END的危险性因素,有一定的临床应用价值。     

胱抑素C水平与急性缺血性脑卒中患者血管内治疗效果的相关性分析

目的 探讨血清胱抑素C(Cystatin C,Cys C)水平对接受血管内治疗的急性缺血性脑卒中患者预后的预测价值。方法 回顾性分析125例接受血管内治疗的急性缺血性脑卒中患者的临床资料,记录相关病史及实验室检验指标水平; 对所有符合血管内治疗标准的急性缺血性脑卒中患者依据美国国立卫生研究院卒中量表(National institutes of health stroke scale,NIHSS)进行神经功能缺损评分; 出院3个月后依据改良Rankin量表(modified rankin scale,mRS)对所有患者进行神经功能评分,依据mRS评分分为2组,mRS评分≤2分为预后良好组,mRS评分>2分为预后不良组,分别比较2组患者的一般资料和手术治疗,并采用Logistic 回归分析确定接受血管内治疗的急性缺血性脑卒中患者预后的不良因素,用受试者工作特征(Receiver operator characteristic,ROC)曲线评估Cys C水平对接受血管内治疗的急性缺血性脑卒中患者的预后不良的预测价值。结果 预后良好组59例,预后不良组66例。预后不良组APTT(Activated partial thromboplastin time,APTT)、入院时Cys C水平、入院时NIHSS评分和年龄较预后良好组高(P<0.05)。多因素Logistic回归分析结果显示入院时NIHSS评分、入院时血清Cys C水平、接受静脉溶栓和APTT水平是接受血管内治疗的急性缺血性卒中患者预后不良的独立危险因素。入院时血清Cys C水平对接受血管内治疗的急性缺血性卒中预后不良的诊断界值为1.005,其敏感度为62.1%,特异度为71.2%,准确度为66.4%。结论 入院时血清Cys C水平对接受血管内治疗的急性缺血性脑卒中患者的不良预后有良好的预测价值,血清Cys C水平越高,预后越差。     

新疆地区颅外颈动脉狭窄的危险因素分析

目的探讨新疆地区颅外颈动脉狭窄的危险因素,为新疆地区颅外颈动脉狭窄的防治提供客观依据,并且有助于缺血性脑卒中的预防。方法收集2011年6月到2014年12月就诊于我院神经内、外科200例颅外颈动脉狭窄的患者,所有患者经头颈部彩超、头颈部CTA或全脑血管造影确诊,同时选择同期在我神经内、外科住院的非颅外颈动脉狭窄的200例患者作为对照;记录所有患者的一般情况和既往史,包括民族(汉、维)、性别、年龄、糖尿病史、高血压史、吸烟史、饮酒史等,患者于住院第二天清晨空腹抽取静脉血,检查血糖(Glu)、低密度脂蛋白(LDL-TC)、高密度脂蛋白(HDL-TC)、甘油三酯(TG)、糖化血红蛋白(Hb A1c)、同型半胱氨酸(Hcy)、超敏c反应蛋白(hs-CRP);组间比较,对14个变量指标先进行单因素Logistic回归分析,调整控制混杂因素,结合专业判断,再将有统计学意义变量纳入方程进行多因素Logistic回归分析,筛选出新疆地区颅外颈动脉狭窄的危险因素。结果变量赋值后经单因素Logistic回归统计分析,在这14个自变量中,年龄、糖尿病史、高血压史、GLU、TG、LDL、HDL、CRP、HCY、Hb A1c这10个自变量有统计学意义,其余4个自变量无统计学意义。通过多因素logistic回归分析可以得出糖尿病史(OR=0.128,95%CI:0.031~0.526)、高血压史(OR=32.154,95%CI:9.587~107.835)、LDL(OR=1.576,95%CI:0.374~0.889)、HCY(OR=1.235,95%CI:1.131~1.350)、Hb A1c(OR=3.218,95%CI:2.316~4.470)5种因素与新疆地区颅外颈动脉狭窄形成相关。结论糖尿病史、高血压病史、LDL、HCY、Hb A1c与颅外颈动脉狭窄具有相关性,是新疆地区颅外颈动脉狭窄的危险因素,在颅外颈动脉狭窄的发生、发展中发挥重要作用。     

急性缺血性脑卒中患者血白细胞计数对短期预后的预测价值

目的分析急性缺血性脑卒中患者外周血白细胞水平对其短期预后的预测价值。方法入选685例急性缺血性脑卒中患者,根据治疗结局分为死亡组(n=30)、残疾组(n=74)、无残疾组(n=581),其中死亡组与残疾组均归为短期预后不良。对3组患者的基线资料(年龄、性别、吸烟史、饮酒史、高血压史、糖尿病、入院时体温等)进行Logistic分析。结果 3组患者年龄、高血糖、高血脂、纤维蛋白原、入院时体温及白细胞计数组间比较,P0.05;单因素Logistic回归分析显示,上述因素均是急性缺血性脑卒中患者发生短期预后不良的预测因素。将年龄等影响因素经校正后,进行多因素Logistic回归分析,结果显示白细胞计数为急性缺血性脑卒中患者发生短期不良结局的独立危险因素,且趋势性P0.05。结论急性缺血性脑卒中患者外周血白细胞计数越高,短期预后越差,临床应引起重视并尽早干预,以改善预后。     

血清脂蛋白相关磷脂酶A2水平与急性缺血性脑卒中患者病情及预后的关系

目的探讨血清脂蛋白相关磷脂酶A2(Lp-PLA2)水平与急性缺血性脑卒中患者病情及预后的关系。方法收集120例急性缺血性脑卒中者和92例健康体检者的一般资料,采用酶联免疫吸附法检测血清LpPLA2水平,于患者入院时采用NIHSS量表评估病情严重程度,于患者出院后3个月采用mRS量表评估预后,分析血清Lp-PLA2水平与患者病情严重程度的相关性,并分析影响患者预后的危险因素。结果急性缺血性脑卒中组患者的高血压比例、血清Lp-PLA2水平明显高于对照组,差异均具有统计学意义(P 0. 05)。120例急性缺血性脑卒中患者中轻度47例、中度38例、重度35例,3组患者的血清Lp-PLA2水平相比差异有统计学意义(P 0. 05)。Pearson相关分析结果显示,血清Lp-PLA2水平与患者NIHSS评分呈正相关(P 0. 05)。120例急性缺血性脑卒中患者中预后良好81例、预后不良39例,预后不良组患者的年龄显著大于预后良好组(P 0. 05)、发病至入院时间显著长于预后良好组(P 0. 05),血清Lp-PLA2水平显著高于预后良好组(P 0. 05)。多因素Logistic回归分析结果显示,年龄、Lp-PLA2是急性缺血性脑卒中患者预后的危险因素(P 0. 05)。结论急性缺血性脑卒中患者血清Lp-PLA2水平越高,则患者的病情严重程度越重,Lp-PLA2是急性缺血性脑卒中患者预后的危险因素。     

Protective action of B1R antagonist against cerebral ischemia-reperfusion injury through suppressing miR-200c expression of Microglia-derived microvesicles

Background and objective: Cerebral ischemia–reperfusion (I/R) injury is a common side-effect for cerebral ischemic disease and its therapeutic regimen is limited. Kinin is pro-inflammatory peptide that is released and acts at the site of injury and inflammation such as brain and it works through bradykinin 1 receptor (B1R). The present study was to examine the effect of B1R antagonist on cerebral I/R injury and the potential mechanism.

Methods: Cerebral I/R injury was induced in mice by transient middle cerebral artery occlusion (MCAO). Neurological function was assessed by Bederson score. Infarct volumes were measured using planimetry. In vitro cell model was made by oxygen-glucose deprivation-Hypoxia/Reoxygenation (OGD-H/R) treatment to N9 microglia cell; and the cultured medium was collected for microvesicles (MVs) isolation and subsequent co-cultured with HT22 cell for sake of assessing their function on neural cell. Relative expression of miR-200c was determined by real time quantitative PCR. Dual luciferase reporter assay was performed to detect the regulatory function of miR-200c to syntaxin-1A.

Results: R715 (B1R antagonist) treatment (500 μg/kg) improves neurologic function after cerebral I/R injury indicated by the decrease of Bederson score and infarct volume. MVs from OGD-H/R treated-N9 cell attenuated neural HT22 cell viability, treatment with LDBK (B1R agonist) accelerated the suppression of HT22 resulted from OGD-H/R; whereas this attenuation was partly weakened by B1R antagonist pretreatment (100 nmol/L). At the same time, B1R antagonist pretreatment caused downregulation of miR-200c in N9 cell and N9-derived MVs, and contributed to syntaxin-1A over expression in HT22 cell. Result of luciferase reporter assay suggested that miR-200c can regulate syntaxin-1A expression. MVs from miR-200c knockdown N9 cells medium had the same effect of B1R antagonist that caused the upregulation of syntaxin-1A and improved OGD-H/R-induced reduction of HT22 cell viability.

Conclusion: Our data suggested that blockage of B1R by B1R antagonist provides neuroprotection action through suppressing signaling delivery of microglia-MVs-miR-200c to neural cell.     

No association between presenilin 1 (PS1) intronic polymorphism and sporadic Alzheimer's disease in Koreans

Summary. To investigate the possible involvement of an intronic polymorphism in the presenilin 1 (PS1) gene and its interactions with the aplolipoprotein E (APOE) or alpha-1 antichymotrypsin (ACT) polymorphisms in the manifestation of AD, we analyzed the PS1, APOE and ACT genotypes of 100 sporadic AD patients and 199 normal elderly controls in Koreans. The genotypic (χ² = 0.92, df = 2, P > 0.1) and allelic (χ² = 0.01, df = 1, P > 0.1) frequencies of the PS1 polymorphism in the late- and early-onset sporadic AD patients did not differ from those in the controls. And the occurrence of the APOE ε4 allele and ACT A allele did not influence the distribution of the PS1 intronic polymorphism. The PS1 intronic polymorphism didn't influence the age-at-onset of AD (F = 0.02, df = 2, P > 0.1). In conclusion, the PS1 intronic polymorphism did not modify the risk for sporadic AD, neither independently nor synergistically with the APOE ε4 allele or ACT A allele, in Koreans. Received December 24, 1999; accepted March 18, 2000     

Human immunodeficiency virus-1 coat protein gp120 impairs contextual fear conditioning: a potential role in AIDS related learning and memory impairments

Many AIDS patients suffer from cognitive impairments including deficits in learning and memory. The Human Immunodeficiency Virus-1 (HIV-1) envelope glycoprotein gp120 is one possible mediator of these impairments. This is because gp120 activates brain microglial cells and astrocytes, and in vivo activation of glia leads to the release of the proinflammatory cytokine interleukin-1 beta (IL-1β). gp120 induced IL-1β release could be involved in producing memory impairments associated with AIDS because central IL-1β activity adversely affects cognitive function. The reported experiments evaluated the effects of i.c.v. gp120 administration and subsequent IL-1β activity on learning and memory processes in the rat. Intracerebroventricular gp120 produced memory impairments on hippocampally dependent contextual fear conditioning, but not hippocampally independent auditory-cue fear conditioning following post-conditioning gp120 administration. Central gp120 administration also caused increases in IL-1β protein levels in the hippocampus and frontal cortex but not in the hypothalamus. gp120 induced memory impairments were blocked by 2 different IL-1 antagonists, alpha melanocyte stimulating hormone (αMSH) and interleukin-1 receptor antagonist (IL-1ra). Finally, heat denaturation of the tertiary structure of gp120 abolished its effects on fear conditioning, suggesting that gp120 impairs contextual fear conditioning by binding to its receptors on glia.     

The role of low-density receptor-related protein 1 (LRP1) as a competitive substrate of the amyloid precursor protein (APP) for BACE1

Cleavage of APP by BACE1 is the first proteolytic step in the production of amyloid-beta (Aβ), which accumulates in senile plaques in Alzheimer's disease. Through its interaction with APP, the low-density receptor-related protein 1 (LRP1) enhances APP internalization. Recently, BACE1 has been shown to interact with and cleave the light chain (lc) of LRP1. Since LRP1 is known to compete with APP for cleavage by gamma-secretase, we tested the hypothesis that LRP1 also acts as a competitive substrate for β-secretase. We found that the increase in secreted APP (sAPP) mediated by over-expression of BACE1 in APP-transfected cells could be decreased by simultaneous LRP1 over-expression. Analysis by multi-spot ELISA revealed that this is due to a decrease in sAPPβ, but not sAPPα. Interaction between APP and BACE1, as measured by immunoprecipitation and fluorescence lifetime assays, was impaired by LRP1 over-expression. We also demonstrate that APP over-expression leads to decreased LRP1 association with and cleavage by BACE1. In conclusion, our data suggest that - in addition to its role in APP trafficking - LRP1 affects APP processing by competing for cleavage by BACE1.     

Polychlorinated biphenyl mixture aroclor 1254-induced oxidative stress plays a role in dopaminergic cell injury

Oxidative stress (OS) is thought to participate in the pathogenesis of neurodegenerative disorders, including Parkinson's disease (PD). Excessive reactive oxygen species (ROS) production can occur during the normal aging process or following exposure to environmental toxicants. Dopamine neurons, which degenerate during PD, are particularly sensitive to oxidative stress. Polychlorinated biphenyls (PCBs), persistent and widespread pollutants, have been shown to adversely impact dopaminergic (DAergic) pathways, but the role ROS play in neurotoxicity remains unclear. To test the hypothesis that PCB exposure compromises dopamine neurons by stimulating ROS production, the direct toxicity and oxidative stress response following PCB exposure was examined both in MN9D dopamine cells and primary mesencephalic cultures. PCBs induced a time- and concentration-dependent increase in ROS production, which preceded cytotoxicity. Whereas intracellular GSH depletion exacerbated PCB effects, antioxidant pretreatment attenuated ROS production and cell death. Coincident alterations in antioxidant defense enzymes also accompanied ROS production, including decreased MnSOD and increased CuZnSOD protein levels. The robust elevation in heme oxygenase-1 levels further support the activation of oxidative stress mechanisms following PCB exposure. Furthermore, PCBs produced concentration-dependent reductions in intracellular dopamine levels and elevated dopamine turnover. Although the intracellular source of ROS remains unknown, these results suggest that sublethal PCB concentrations activate an oxidative stress-related pathway, which potentially disrupts dopamine neuron function.     

脑梗死患者血清胰岛素活性与PAI—1关系的探讨

目的 论证脑梗死患者存在胰岛素抵抗（IR），探讨IR与血浆纤溶酶原激活物抑制物－1（PAI－1）活性在脑梗死形成中的可能关系。方法 选择47例正常成年人（I组）、48例脑梗死患者（Ⅱ组）、42例脑梗死伴Ⅱ型糖尿病患者（Ⅲ组），分别测定血清胰岛素（IS）、C肽水平及血浆PAI－1、组织纤溶酶原激活物（t-PA）活性。结果 （1）Ⅱ、Ⅲ组患者IS、C肽、PAI－1活性明显高于Ⅰ组。其中以Ⅲ组增高最明显。（2）Ⅱ组、Ⅲ组IS、C肽与PAI－1及IS与C肽间呈正相关。结论 （1）IR可能参与了脑梗死的发生。（2）脑梗死血浆PAI－1活性增高与IS及C肽呈正相关，PAI－1活性增高导致血浆纤溶活性降低，可能是IR引起脑梗死的中间环节。（3）IR及PAI－1活性增高可能是糖尿病并发脑梗死的原因之一。     

Presynaptic protein synaptotagmin1 regulates the activity‐induced remodeling of synaptic structures in cultured hippocampal neurons

Activity‐dependent reorganizations of central neuronal synapses are thought to play important roles in learning and memory. Although the precise mechanisms of how neuronal activities modify synaptic connections in neurons remain to be clarified, the activity‐induced neuronal presynaptic proteins such as synaptotagmin1 may contribute to the onset of synaptic remodeling. To understand better the physiological roles of synaptotagmin1, we first examined the prolonged effects of neuronal stimulation capable of inducing synaptotagmin1 on the distribution of a postsynaptic proteins (PSD) protein Homer1c by immunostaining. Previously we found that glutamate stimulation induced other postsynaptic proteins, such as postsynaptic density‐95 (PSD95), a biphasic change with an initially diffuse distribution after 30 min to 1 hr, followed by reassembly to more than the original level after 4–8 hr, suggesting that glutamate stimulation induces a global biphasic alteration in synaptic structures. To dissect further the functions of synaptotagmin1 in the activity‐induced synaptic remodeling, short hairpin RNA (shRNA) vectors that specifically block the expression of endogenous synaptotagmin1 were constructed. When the shRNA of synaptotagmin1 was introduced to the neurons, the activity‐induced changes were almost completely suppressed. We found that synaptotagmin1 contributes to the postsynaptic remodeling in a retrograde manner. Our data indicate that synaptotagmin1 regulates the activity‐induced biphasic changes of post‐ and presynaptic sites. © 2013 Wiley Periodicals, Inc.     

TNF-α作用于小鼠脑血管内皮细胞产生IL-1、ET受体机制

目的体外培养野生型小鼠脑血管内皮细胞(BVEC)和TNF1型受体敲除的小鼠BVEC/TNFRI(-/-),给予一定量肿瘤坏死因子-α(TNF-α)刺激后,观察两种细胞不同时间点产生白介素-1(IL-1)、内皮素(ET)受体水平的变化。方法体外培养小鼠BVEC和野生型小鼠BVEC,分别给予相同浓度TNF-α刺激1、6、12、24h后,用放免法检测两种细胞刺激前后IL-1、ET产生量。结果给予TNF-α刺激后,仅有野生型脑内皮细胞IL-1、ET产生量明显增高,BVEC/TNF-RI(-/-)型脑内皮细胞刺激前后IL-1、ET产生量无明显变化。结论TNF-αⅠ型受体主要参与介导小鼠BVEC IL-1、ET的表达。