肾素-血管紧张素系统与阿尔茨海默病

肾素-血管紧张素系统(RAS)是一循环内分泌系统,脑内存在RAS活性,目前关于RAS在脑内定位、以及与阿尔茨海默病(AD)相关的遗传学和分子生物学研究已取得了一定进展。文章综述了RAS与AD的关系,并从血管紧张素转化酶抑制剂(ACEI)、血管紧张素II受体1阻滞剂(ARB)类降压药物在AD中的临床应用等方面总结了RAS在AD中的研究进展。     

不同部位、范围急性脑血管病患者肾素-血管紧张素系统的变化

目的研究肾素(RA)、血管紧张素Ⅱ(AⅡ)、醛固酮(ALD)在不同部位、范围的急性脑血管病(ACVD)患者中的含量及其作用.方法采用放射免疫法测定236例ACVD患者及63名正常对照者血浆RA、AⅡ、ALD含量.结果不同部位ACVD患者血浆RA、AⅡ、ALD含量较正常对照组显著升高(P<0.01).不同部位脑出血时,血浆RA、AⅡ、ALD含量比较呈丘脑>基底节>脑叶,有显著性差异(P<0.01).不同部位急性脑梗死时,以大脑中动脉系梗死RA、AⅡ、ALD含量最高,与丘脑梗死组、基底节梗死组及脑叶梗死组比较有显著性差异(P<0.01～0.05),而后3组之间RA、AⅡ、ALD含量比较无显著性差异(P>0.05).ACVD不同病损范围,血浆RA、AⅡ、ALD含量随着脑损伤范围增大而增高.结论肾素-血管紧张素-醛固酮系统(RAS)改变与不同部位、范围ACVD密切相关,测定血浆RA、AⅡ、ALD含量, 对临床监测ACVD患者病情,判断预后及提高治疗效果有积极的意义.     

肾素-血管紧张素系统与脑出血关系的探讨

近年来 ,随着神经内分泌学研究的进展 ,肾素 -血管紧张素系统在脑出血中的作用受到重视。本文应用放免分析法 ,同步监测脑出血患者肾素活性 RA、血管紧张素 A 、醛固酮AL D含量 ,力求为脑出血患者病情、预后及提高治疗建立新途径。资料方法1.研究对象 :10 6例脑出血住院患者均符合全国第 2届脑血管疾病会议修订的诊断标准并经头颅 CT证实。年龄 2 7～79岁 ,男 5 0例 ,女 5 6例。对照组 6 3例健康成人无其他疾患 ,男 30例 ,女 33例 ,年龄 32～ 73岁。2 .研究方法 :病例组在发病三天内 (急性期 )及发病三周后 (恢复期 ) ,对照组在晨起静…     

中枢神经系统的肾素—血管紧张素系统

本文介绍了中枢神经肾素—血管紧张素系统在脑内的分布情况,简要综述了血管紧张素Ⅱ在体液调节、中枢加压及其与心房利钠多肽的关系等方面的意义。     

肾素-血管紧张素系统干预与阿尔茨海默病

阿尔茨海默病(AD)是一种以β淀粉样蛋白异常沉积和tau蛋白异常磷酸化为典型病理学改变的神经退行性疾病,是最常见的痴呆类型。肾素-血管紧张素系统(RAS)为体内重要的心血管调节系统,近来研究证实脑内存在独立的RAS;自从研究发现血管紧张素转换酶(ACE)基因多态性与AD发病相关以来,RAS与AD神经生理学关系得到进一步深入研究,越来越多的研究也进一步证实了RAS影响AD的发病和进展。     

肾素-血管紧张素-醛固酮系统与脑血管病的研究进展

自从1898年Tigerstedt R等发现肾素和1939年Braun-Menendez E等发现血管紧张素以来,对肾素-血管紧张素-醛固酮系统(RAAS)的研究已有近百年的历史,但随着生物技术的飞速发展,RAAS新的成员、新的受体、新的调节物和新的药物等不断问世.RAAS作为心血管系统最重要、历史最久的活性物质早已被公认,近年的研究又发现它可引起脑水肿的发生,加重缺血性脑组织的损害[1].RAAS与脑血管病转归与预后的关系已逐渐引起人们的重视.本文就RAAS的研究现状、RAAS与脑血管病及其并发的多脏器功能衰竭(MOF)的研究进展做一综述.     

组织型肾素—血管紧张素系统与脑

肾素一血管紧张素系统（renin-angiotensin system,RAS）是一重要的循环内分泌系统。近年来越来越多的研究表明,人体许多组织还存在着非血源性的组织型RAS,并在人体的病理生理过程中发挥着重要作用。本文复习近年来有关脑RAS的研究情况,对RAS各成分在脑中的分布特点、传递方式及脑RAS的功能进行综述。     

不同部位、范围急性脑血管病患者紧奏—血管紧张素系统的变化

目的研究肾素(RA)、血管紧张素Ⅱ(AⅡ)、醛固酮(ALD)在不同部位、范围的急性脑血管病(ACVD)患者中的含量及其作用.方法采用放射免疫法测定236例ACVD患者及63名正常对照者血浆RA、AⅡ、ALD含量.结果不同部位ACVD患者血浆RA、AⅡ、ALD含量较正常对照组显著升高(P<0.01).不同部位脑出血时,血浆RA、AⅡ、ALD含量比较呈丘脑>基底节>脑叶,有显著性差异(P<0.01).不同部位急性脑梗死时,以大脑中动脉系梗死RA、AⅡ、ALD含量最高,与丘脑梗死组、基底节梗死组及脑叶梗死组比较有显著性差异(P<0.01～0.05),而后3组之间RA、AⅡ、ALD含量比较无显著性差异(P>0.05).ACVD不同病损范围,血浆RA、AⅡ、ALD含量随着脑损伤范围增大而增高.结论肾素-血管紧张素-醛固酮系统(RAS)改变与不同部位、范围ACVD密切相关,测定血浆RA、AⅡ、ALD含量, 对临床监测ACVD患者病情,判断预后及提高治疗效果有积极的意义.     

肾素-血管紧张素系统阻断药物在抗高血压治疗中的应用

过去20余年，肾素-血管紧张素一醛固酮（renin-angiotensin-aldosteron，RAA）系统被认为在高血压、心血管疾病和心。肾疾病的发病中占有重要地位。而。肾素一血管紧张素一醛固酮轴已变为药理学干预的重要靶点，其中积累最多的药物治疗经验当首推血管紧张素转换酶抑制药（ACEI）。1981年问世的血管紧张素转换酶抑制药卡托普利（captopril）以其抑制转换酶使血管紧张素Ⅰ（AngⅠ）不能转变为血管紧张素Ⅱ（AngⅡ），从而达到降低血压的目的而受人瞩目。如今被认可的血管紧张素转换酶抑制药已有10种（表1）。其后，1995年首次公布的血管紧张素Ⅱ受体阻断药（angiotensin Ⅱ receptorblocker，ARB）氯沙坦（losartan）以其对肾素-血管紧张素-醛固酮轴新的干预靶点而受到医学界的关注，近年来对血管紧张素Ⅱ受体阻断药的开发更为迅速。此外，这类药物还被确认具有降低血压以外的靶器官保护作用，尤其是具有延缓进行性心、肾血管性疾病的病程，从而使其临床应用适应证从高血压扩展到充血性心力衰竭、心肌梗死后和糖尿病性。肾病等领域。笔仅对目前最常用的肾素-血管紧张素系统（renin—angioten-sinsystem，RAS）阻断药在高血压治疗中的应用进行阐述，而对于醛固酮及阻断其受体的药物则归于利尿药中叙述。     

肾素-血管紧张素系统在中枢神经系统疾病中的研究进展

<正>近年来,中枢神经系统疾病发病率逐年上升,数据显示,我国每年新发卒中150～200万例,其中缺血性脑卒中占80%以上;过去20 y,抑郁的发病人群增加近50%,目前全球患病人数近3亿~([1]);保守预计2050年全球阿尔茨海默病(Alzheimer disease,AD)的发病率将上升3倍,这些疾病均严重威胁人类健康及生命安全。目前,对于神经系统疾病的治疗方法有限,效果欠佳,因此寻找新的治疗突破点尤为迫切。肾素-血管紧张素系统(rennin-angiotensin system,RAS)是重要的血压和水电解质平衡调节系统。近年来研究发现高血压是AD发生发展的重要危险因素,控制血压可明显改善认知功能障碍~([2]),ACEI或ARB药物可通过调节血压或透     

激肽释放酶-激肽系统及其与急性缺血性脑血管病的关系

激肽释放酶-激肽系统(kallikreinkinin system,KKS)又称激肽系统,广泛存在于动物体内的多个系统,尤其是在心血管系统内分布更为密集.其主要成分为:激肽原(活性因子前体)、激肽释放酶(活性因子前体的激活物,又称为激肽原酶)、激肽(主要活性因子)、激肽酶(活性因子的灭活物).     

Vasopressin release after enhanced serotonergic transmission is not due to activation of the peripheral renin-angiotensin system

Pharmacological enhancement of 5-hydroxytryptamine (5-HT) transmission increases plasma vasopressin in rats. To investigate whether this effect is mediated through activation of the peripheral renin-angiotensin system, plasma vasopressin concentrations were measured after 5-HT activation in rats with lesions of the subfornical organ or pretreated with saralasin. The results show that the 5-HT-induced elevation of vasopressin is not due to activation of the peripheral renin-angiotensin system.     

Heart rate variability in ischemic heart disease

Major untoward events, such as life-threatening arrhythmias and acute coronary events, have been suggested to be triggered by the activation of the autonomic nervous system in patients with coronary artery disease. Analysis of heart rate variability by conventional time and frequency domain methods, as well as by newer methods derived from nonlinear system theory, has offered a novel approach for studying the abnormalities in cardiovascular neural regulation in ischemic heart disease. Heart rate variability has been shown to be altered among patients with ischemic heart disease as compared to their age-matched controls without the evidence of ischemic heart disease. There are also obvious differences in various measures of heart rate variability between patients with uncomplicated coronary artery disease and those with coronary artery disease with complicated myocardial infarction. Impaired high-frequency oscillations of heart rate is the most prominent feature in patients with uncomplicated coronary artery disease, suggesting mainly an impairment in vagal autonomic regulation. Patients with prior myocardial infarction have a reduced overall heart rate variability, and a specific spectral pattern with a reduced low-frequency spectral component has been observed in patients with prior myocardial infarction and impaired left ventricular function. Recent studies have shown that the new nonlinear measures, particularly fractal analysis methods of heart rate dynamics, can detect subtle changes in heart rate behavior that are not easily detected by traditional analysis methods from ambulatory recordings. Patients with prior myocardial infarction have steeper power-law slope analyzed from the ultra and very low-frequency spectral bands, and they also have more random short-term heart rate dynamics analyzed by the detrended fluctuation method. A large body of data indicate that reduced overall heart rate variability is associated with an increased risk of mortality and nonfatal cardiac events in patient with ischemic heart disease. Of particular note, recent studies indicate that fractal analysis methods perform even better than the traditional analysis methods of heart rate variability as predictors of death and the onset of life-threatening arrhythmic events in post-infarction populations. These findings support the notion that heart rate variability analysis methods, such as fractal and complexity measures as well as conventional techniques, give valuable clinical information among patients with ischemic heart disease.     

Important roles for angiotensin III and IV in the brain renin-angiotensin system

Considerable evidence now suggests that the precursors and enzymes necessary for the formation and degradation of biologically active forms of angiotensins are present in brain tissues, accompanied by at least three specific binding sites. It also appears that several forms of angiotensin may serve as signaling agents at these sites. There is accumulating support for the notion that AngII must be converted to AngIII in order to bind at the AT₁ and AT₂ receptor subtypes, and AngIII must be converted to AngIV in order to activate the AT₄ receptor subtype. Further, AngII(1–7) may activate a separate binding site concerned with antidiuresis, however, characterization of this site has not been completed. The AT₁ site appears to mediate the classic angiotensin functions concerned with body water balance, maintenance of blood pressure, and cyclicity of reproductive hormones and sexual behaviors. This receptor site also exerts some control over the secretion of pituitary hormones. Less is known about the functional importance of the AT₂ site, however, it has been implicated in vascular growth, control of blood flow, and perhaps modulation of NMDA receptors. The AT₄ site is heavily distributed in neocortex, hippocampus, cerebellum, and basal ganglia structures, as well as several peripheral tissues. This site appears to mediate memory acquisition and retrieval, the regulation of blood flow, neurite outgrowth, angiogenesis, and kidney function. In addition to the well-studied functions of the brain renin-angiotensin system, additional less well investigated responses are reviewed. These include electrophysiological activation, tachyphylaxis, long term potentiation, learning and memory, and cognitive affect.     

内质网应激在缺血性脑血管病中的作用

缺血性脑血管病损伤过程极为复杂．其发病机制涉及脑组织能量代谢紊乱、兴奋性氨基酸毒性、细胞内钙超载、自由基损伤、神经细胞凋亡、炎症反应等多个环节。在脑梗死神经元损伤中氧化应激和内质网应激可同时或相继发生。钙是两者相互联系的纽带，最终导致神经损伤。内质网是细胞加工蛋白质和贮存钙的主要场所，它对缺血、缺氧及钙平衡紊乱极为敏感，可导致内质网应激并激活多条信号通路。内质网应激决定了细胞的转归，如抵抗、适应、损伤或凋亡。[第一段]     

血管生成素与缺血性脑血管病

血管生成素（ANG）具有促血管生成作用,本文着重阐述ANG的生理作用及其促血管生成的机制,重点介绍缺血性脑血管病（ICVD）时ANG的表达及其对ICVD的保护及治疗作用。     

血管紧张素Ⅳ：治疗阿尔茨海默病的潜在靶点

诸多证据提示脑内肾素-血管紧张素系统（RAS）与阿尔茨海默病（AD）有着密切关系.血管紧张素Ⅳ（AngⅣ）作为脑内RAS的成员之一,能促进乙酰胆碱释放,抑制胰岛素调节性氨基肽酶（IRAP）,从而减少其对促认知神经肽的降解,同时增强神经元对葡萄糖的摄取和利用,进而提升动物的学习记忆能力,有望成为治疗AD相关认知功能障碍的新靶点.文中就AngⅣ和IRAP的生理学特性、与认知功能的关联以及临床应用所面临的问题进行综述.     

多系统萎缩与帕金森病的早期鉴别诊断

目的　为多系统萎缩 (m ultiple system atrophy,MSA)与帕金森病 (Parkinson disease,PD)的鉴别诊断提供依据。方法　对 12名首发锥体外系症状的 MSA患者和 40名 PD患者的临床症状及主要辅助检查行比较分析。MSA诊断依据 Quinn(1994)提出的临床诊断标准。PD诊断参考英国帕金森病协会 1997年提出的诊断标准。结果　与 PD患者比较 ,MSA患者发病年龄较小 (5 4.3 2± 9.5 0 vs 61.5 6± 9.5 5 ,P<0 .0 5 ) ,主要以行动困难或僵硬为首发症状 (66.7% vs 2 5 % ,P<0 .0 5 ) ;少数以震颤为首发症状 (3 3 .3 % vs 75 % ,P<0 .0 5 ) ,也可以单侧症状发病(5 8.3 % vs 80 % ,P>0 .0 5 ) ,多数对多巴胺反应不良 (66.7% vs 2 0 % ,P<0 .0 5 ) ,植物神经症状、语言障碍比 PD患者显著多见 (分别为 83 .3 % vs 2 5 % ;5 0 % vs12 .5 % ;P<0 .0 5 )。辅助检查 :MRI:大部分 MSA患者有阳性表现 ,橄榄体、脑桥和小脑部位有萎缩 ,PD患者未发现特征性病变。 PET:3例 MSA患者均呈阳性表现。神经心理 :MSA患者未出现智能障碍的情况 (0 % ) ,少数 PD(10 % )患者出现智能障碍 ,但两者比较无统计学意义 (P>0 .0 5 )。结论　依据详细的病史和全面的神经系统查体 ,并结合临床辅助检查 ,可提高 MSA和 PD早期鉴别诊断的准确性     

The cholinergic system and Parkinson disease

Although Parkinson disease (PD) is viewed traditionally as a motor syndrome secondary to nigrostriatal dopaminergic denervation, recent studies emphasize non-motor features. Non-motor comorbidities, such as cognitive impairment, are likely the result of an intricate interplay of multi-system degenerations and neurotransmitter deficiencies extending beyond the loss of dopaminergic nigral neurons. The pathological hallmark of parkinsonian dementia is the presence of extra-nigral Lewy bodies that can be accompanied by other pathologies, such as senile plaques. Lewy first identified the eponymous Lewy body in neurons of the nucleus basalis of Meynert (nbM), the source of cholinergic innervation of the cerebral cortex. Although cholinergic denervation is recognized as a pathological hallmark of Alzheimer disease (AD), in vivo neuroimaging studies reveal loss of cerebral cholinergic markers in parkinsonian dementia similar to or more severe than in prototypical AD. Imaging studies agree with post-mortem evidence suggesting that basal forebrain cholinergic system degeneration appears early in PD and worsens coincident with the appearance of dementia. Early cholinergic denervation in PD without dementia appears to be heterogeneous and may make specific contributions to the PD clinical phenotype. Apart from well-known cognitive and behavioral deficits, central, in particular limbic, cholinergic denervation may be associated with progressive deficits of odor identification in PD. Recent evidence indicates also that subcortical cholinergic denervation, probably due to degeneration of brainstem pedunculopontine nucleus neurons, may relate to the presence of dopamine non-responsive gait and balance impairments, including falls, in PD.     

数字减影血管造影在缺血性脑血管病检查及治疗中的价值

目的探讨数字减影血管造影(DSA)在缺血性脑血管病检查及治疗中的价值。方法回顾性分析325例反复发作的短暂脑缺血发作或脑梗死患者的脑血管造影检查结果,结合临床症状及磁共振血管成像(MRA)进行对比。结果DSA未见明显异常18例,单纯颅外动脉狭窄163例,单纯颅内动脉狭窄76例,同时存在颅内外多发狭窄和(或)闭塞68例,83例接受了介入治疗。支架成形术后脑实质染色增加、循环时间缩短。结论全脑DSA检查是缺血性脑血管病诊断的"金标准",与MRA相比更能明确病变部位、形态、性质及侧枝循环情况,是介入干预前的必备手段,对评估支架成形术前术后血液动力学变化优于其他影像检查。