Angiofensin converting enzyme density is increased in temporal cortex from patients with Alzheimer's disease

The present study assesses the binding density of the selective angiotensin converting enzyme (ACE) radioligand [³H]ceranapril in brain tissue homogenates derived from patients with Alzheimer's disease and those from age-, sex- and post-mortem delay-matched neurologically normal patients. Saturation studies with [³H]ceranapril identified that the specific binding (defined by captopril, 10 μM) was homogenous and of high affinity. ACE inhibitor recognition site density was higher by some 70% in the temporal cortex (Brodmann area 22) from Alzheimer's patients whereas densities were similar in frontal cortex and cerebellum when compared to control tissue. It is unknown whether this apparently selective alteration in ACE density is directly related to. or a compensatory effect of the disease, but it provides additional support for the development of compounds which interact with the central angiotensin system as novel therapies for cognitive dysfunction.     

内皮素转换酶基因在急性脑梗死患者外周血中的表达及临床其意义

目的 观察急性脑梗死(ACI)患者血内皮素转换酶(ECE)mRNA的表达及其临床意义.方法 检测40例发病72h内的ACI患者及28名正常对照者血ECE mRNA表达值(半定量RT-PCR法)及内皮素(ET)-1含量,并对两者的关系及其与入院时欧洲卒中评分(ESS)、既往史、年龄、血糖、血脂的关系进行分析.结果 (1)ACI组和正常对照组血细胞ECE mRNA表达值分别为0.31±0.09、0.25±0.10,差异有统计学意义(f=2.46,P＜0.05);(2)ACI组血浆ET-1水平[(183.27±56.63)pg/ml]显著高于正常对照组[(156.47±34.24)pg/ml](t=2.23,P＜0.05);(3)正常对照组ECE mRNA表达值与血浆ET-1含量呈负相关(r=-0.452,P＜0.05),而ACI组两者无相关性(r=0.143,P＞0.05);(4)分别将ACI组伴与不伴高血压、糖尿病、脑卒中史患者的血ECE mRNA表达值、血浆ET-1含量进行比较,差异无统计学意义;(5)ACI组血ECEmRNA表达值、血浆ET-1含量与年龄、ESS、空腹血糖及血脂无相关性.结论 ACI患者血ECE mRNA表达上调,可能参与了ACI的发病机制;ET-1与ECE之间可能存在生理性下调和病理性上调;影响ECE mRNA表达的因素复杂多样,其与脑卒中常见危险因素的关系有待进一步研究.     

The effect of the converting enzyme inhibitor HOE 498 on the renin angiotensin system of normal volunteers

Summary The converting enzyme inhibitor HOE 498 was evaluated in 12 normotensive male volunteers aged 21 to 26. The efficacy of single 5, 10 or 20 mg oral doses in blocking the pressor response to exogenous angiotensin I was tested in 3 of the subjects. All 3 doses of HOE 498 reduced the pressor response to exogenous angiotensin I to below 50% of control within 1,5 h following administration of the drug. Plasma renin and converting enzyme activity, blood angiotensin I, as well as plasma angiotensin II and aldosterone were measured serially before and up to 72 h following oral administration of a single dose of 2.5, 5, 10 or 20 mg of HOE 498 to groups of 5 volunteers each. As expected, blood angiotensin I levels and plasma renin activity rose while plasma converting enzyme activity, plasma angiotensin II and aldosterone concentration fell after administration of the drug. While the dose of 2.5 mg did not reduce plasma converting enzyme activity below 20% of control, the higher doses all resulted in plasma converting enzyme inhibition exceeding 90%. No side-effects were observed. It is concluded that in normal volunteers HOE 498 is an effective potent and long-acting converting enzyme inhibitor. Based on these preliminary findings it is expected that 5 mg HOE 948 will turn out to be adequate for therapeutic use.     

慢性缺氧对大鼠血清中血管紧张素转换酶活性的影响

本文报道缺氧敏感大鼠(HT)和普通大鼠(W)在模拟5000米高原的减压缺氧环境下,血清血管紧张素转换酶(ACE)活性和机体适应能力的关系。HT和W大鼠血清ACE活性分别在缺氧10,20天时下降到最低值,继而回升。HT大鼠变化明显。二者的动脉血压与ACE活性变化趋势基本一致,反映血清ACE在机体对抗缺氧环境中起一定的调节作用。缺氧性肺动脉高压与ACE活性的关系不明。     

A double-blind comparison of perindopril and hydrochlorothiazide-amiloride in mild to moderate essential hypertension

The aim of this 3-month double-blind multicenter trial was to compare the antihypertensive efficacy and tolerability of the ACE inhibitor perindopril with those of a diuretic combination. After 1 month of receiving placebo, 165 patients with essential hypertension were randomised to perindopril 4 mg (n = 82) or to 50 mg hydrochlorothiazide + 5 mg amiloride (n = 83). The patients were treated for 3 months with monthly assessments, "uncontrolled" patients (DBP greater than 90 mm Hg) had their dosage doubled and then, if necessary, atenolol 50 mg was added. At the end of the 3-month study, mean decreases in supine and standing systolic and diastolic blood pressures were similar in both groups. In the perindopril group, BP control was obtained in 56% of the patients with the 4 mg dosage and required an increase to 8 mg alone in 16% and with atenolol in 5%. The corresponding percentages in the diuretic group were 48, 23 and 13%. The overall percentage of "controlled" patients was similar in the 2 groups, respectively 78 and 84%. The nature and incidence of complaints were comparable in the 2 groups. Adverse laboratory changes were more frequent in the diuretic group: decrease in blood sodium (140.5 vs 139.1 mmol/l; P less than 0.01), potassium (4.2 vs 3.9 mmol/l; P less than 0.01) with 10 patients having significant hypokalemia, increase in blood urea, triglycerides and uric acid. By contrast, a transient increase in blood potassium with a decrease in triglycerides was observed in the perindopril group.     

ACE基因插入/缺失多态性与妊娠期高血压疾病发病关系的Meta分析

目的:探讨不同人群中血管紧张素I转换酶(ACE)基因插入(I)/缺失(D)多态性与妊娠期高血压疾病发病的关系。方法:检索Pub Med、Cochrane、清华同方、重庆维普,时间从该数据库建立至2016年10月1日。全面收集有关妊娠期高血压疾病发病与ACE I/D基因多态性相关的研究文献,制定文献纳入及排除标准。应用Revman 5.1软件进行Meta分析,计数资料采用优势比(OR)及其95%CI表示。结果:纳入63篇符合条件的研究文献,其中42篇是对亚洲人群的研究,20篇是对欧洲人群的研究,1篇是非洲人群的研究,共纳入妊娠期高血压疾病患者12030例(病例组),健康正常人群14090例(对照组)。Meta分析结果显示,在总体人群、亚洲人群和欧洲人群中,D等位基因、DD基因型以及II基因型在病例组和对照组分布的差异性,D等位基因OR分别为1.42、1.47、1.34,P0.00001、P=0.0004、P0.0001;DD基因型OR分别为1.62、1.67、1.56,P0.00001、P=0.0007、P0.00001;II基因型OR分别为0.72、0.68、0.81,P=0.0003、P=0.002、P=0.10。结论:ACE D等位基因和DD基因型同妊娠期高血压疾病发病关系密切。在总体人群和亚洲人群中,II基因型是妊娠期高血压疾病发病的一种保护性因素;而欧洲人群未发现有关系。     

不稳定型心绞痛患者血管紧张素转换酶基因多态性与中医证型及冠状动脉斑块性质的关系

目的观察不同中医证型及冠状动脉斑块性质的不稳定型心绞痛患者血管紧张素转换酶（ACE）基因多态性分布规律。方法收集240例不稳定型心绞痛患者,气虚血瘀证38例,气滞血瘀证24例,痰阻心脉证19例,心血瘀阻证39例,阴寒凝滞证18例,气阴两虚证23例,心肾阴虚证32例,阳气虚衰证47例。另收集健康志愿者60例作为对照。采用聚合酶链反应（PCR）技术检测其ACE等位基因插入/缺失（I/D）及ACE基因型,采用多层螺旋CT判断冠状动脉斑块的硬化程度,分析不同中医证型及冠状动脉斑块性质的不稳定型心绞痛患者ACE基因多态性分布规律。结果240例不稳定型心绞痛患者冠状动脉软斑块者120例、中等密度斑块者54例、钙化斑块者66例。不稳定型心绞痛患者ACE-DD基因型者32.9%（79例）,显著高于健康志愿者的15%（9例）（P<0.05）;不稳定型心绞痛患者D等位基因者54.2%（130例）,较健康志愿者的46.7%（28例）显著升高（P<0.05）。气虚血瘀证、痰阻心脉证、心血瘀阻证患者中DD基因型分布显著高于健康志愿者（P<0.01）,气滞血瘀证、气阴两虚证患者中ACE-ID基因型分布显著高于健康志愿者（P<0.01）。心血瘀阻证、痰阻心脉证、气阴两虚证患者中D等位基因染色体数显著高于健康志愿者（P<0.01）。冠状动脉软斑块者与中等密度斑块者ACE-DD基因型比例均显著高于钙化斑块者（P<0.05）。结论ACE基因DD基因型及D等位基因可能是冠心病不稳定心绞痛的易感基因,且在中医辨证之气虚血瘀证、痰阻心脉证、心血瘀阻证患者中分布较多,ACE-DD基因型在软斑块及中等密度斑块患者中分布较多。     

贝那普利对糖尿病大鼠视网膜微血管病变的保护作用

目的:探讨贝那普利(benazepril,BZ)对糖尿病大鼠视网膜微血管病变的保护作用及机制。方法:链脲佐菌素ip制备糖尿病大鼠模型,分为糖尿病组(DM)、贝那普利治疗组(BZ),同时设立正常对照组(Con)。治疗组每天灌胃给予BZ10mg/kg。24wk后放射免疫法测定血浆AngⅡ水平,免疫组织化学法和Westernblot技术检测视网膜VEGF蛋白表达,透射电镜观察视网膜血管基底膜厚度变化。结果:与Con组相比,DM组大鼠血浆AngⅡ水平明显增高(P<0.01),视网膜VEGF蛋白表达显著增强(P<0.01),视网膜微血管基底膜明显增厚;与DM组相比,BZ治疗后大鼠血浆AngⅡ水平明显降低(P<0.05),视网膜VEGF蛋白表达则显著减弱(P<0.01),视网膜微血管基底膜增厚明显减轻。结论:BZ可通过抑制血浆AngⅡ水平,减少糖尿病大鼠视网膜组织VEGF表达,抑制视网膜微血管基底膜增厚。     

组织肾素-血管紧张素系统在血管球囊损伤后内膜增生中的作用

目的 :探讨组织肾素 -血管紧张素系统 ( RAS)在血管球囊损伤后内膜增生中的作用。方法 :用放射免疫法测定血管球囊损伤后大鼠的血浆肾素活性 ( RA)、血管紧张素 ( Ang ) ;用生物化学方法检测血清和组织血管紧张素转换酶 ( ACE)活性 ;免疫组化法观察血管壁细胞增殖过程。结果 :损伤后循环中 RAS各成分无明显变化 ,球囊损伤后第 3天组织中 ACE活性增高 ( P <0 .0 1) ,第 14天达最高 ,第 2 8天降至基础水平。ACE活性与 PCNA阳性细胞数呈正相关。ACE抑制剂 Perindopril抑制组织中 ACE活性 ,减少内膜增生。结论 :组织 RAS而非循环 RAS在血管球囊损伤后内膜增生中起重要作用。通过抑制组织 ACE活性可以预防血管成形术后再狭窄。     

TACE在自体髓核移植背根节致根性神经痛中的作用机制研究

目的:探讨TACE在椎间盘突出致坐骨神经痛发病机制中的作用。方法:采用自体髓核移植至L4、5神经节,建立根性神经痛的动物模型,应用VonFrey针丝及RTY-Ⅰ型热痛测仪对神经行为的改变进行检测,采用免疫组化法检测TACE在神经节及神经根中的表达,采用RT-PCR的方法检测TACE和TNF-αmRNA表达,并分析其与神经行为改变之间的相关性。结果:自体髓核移植可以导致明显的机械刺激痛觉过敏现象,而无明显的热刺激痛觉过敏,TACE在自体髓核移植术后4d表达开始增强（P<0.05）,术后1周表达最强（P<0.01）,术后3周逐渐恢复正常,与TNF-α的表达及TACE的表达之间存在显著相关性。结论:TACE作为释放活性TNF-α的特异性蛋白酶,自体髓核移植至DRG后,其蛋白表达升高,TNF-αmRNA、TACEmRNA表达之间存在线性相关,说明TACE可能是抗TNF-α治疗的新靶点,在治疗椎间盘突出引起的根性神经痛中具有重要作用。