血管紧张素转换酶抑制剂抑制血管平滑肌细胞增殖的机制

目的: 探讨血管紧张素转换酶抑制剂(ACEI)抑制动脉平滑肌细胞增殖及向内膜迁徙的机理。方法: 球囊导管损伤Wistar大鼠颈总动脉, 实验组于术前2 d开始给与ACEI(temocapril-HCl 10 mg·kg^-1·d^-1), 术后2 d、3 d、5 d分批处死。用抗人PDGF-A、-B及其受体, 抗人MMP-1、MMP-9等抗体以ABC法行免疫染色。动脉组织行放射自显影乳剂原位酶谱分析。电镜下观察细胞质内小器官及细胞周围弹性、胶原纤维的密度。结果: 给ACEI后, PDGF及其受体、MMP-1、-9蛋白阳性细胞率及明胶酶活性显著降低, 并抑制了中膜平滑肌细胞的表型转换。结论: ACEI可能通过继发地抑制PDGFs、MMPs蛋白表达, 阻碍细胞表型转换, 从而阻止中膜平滑肌细胞增殖及向内膜迁徙。     

血管紧张素转换酶2研究进展

肾素-血管紧张素系统(renin-angiotensin sys-em,RAS)是一个非常古老而复杂的调节系统,低等生物如酵母菌即有完整的RAS。在哺乳类动物,RAS不仅对水盐代谢、维持血压稳定起重要作用,而且还是心血管、泌尿、生殖等系统发育和功能调节的一个重要系统;在炎症反应、损伤的修复、愈合及造血等病理生理过程中亦起重要作用。血管紧张素转换酶(angiotensin convertingenzyme,ACE)是血管紧张素合成主要的限速酶,是RAS的枢纽。随研究的不断深入,发现RAS的复杂程度远远超出人们的想象,尽管对它的研究已超过了100年,但对RAS的认识才刚刚开始。20…     

血管紧张素ⅡⅠ型受体拮抗剂和血管紧张素转换酶抑制剂的肾保护作用及其对肾内肾素-血管紧张素系统的影响

目的:比较血管紧张素受体拮抗剂(AT₁RA)和血管紧张素转换酶抑制剂(ACEI)的肾脏保护作用,观察这两类药物对肾脏局部肾素-血管紧张素系统的影响。方法:肾病综合征模型由反复给SD大鼠腹腔注射嘌呤霉素诱导而成。28只大鼠随机分为4组:正常对照组、肾病对照组、AT₁RA治疗组和ACEI治疗组。12周后收集血、尿和肾组织标本进行检测。结果:两治疗组尿蛋白明显少于肾病对照组,且到实验期末,肾功能仍在正常范围,肾小球和肾间质损伤指数也低于肾病对照组,但两治疗组间无明显差异(P＞0.05)。肾病对照组的肾组织ACE活性、血管紧张素Ⅱ浓度显著高于正常对照组(P＜0.01)。在ACEI和AT₁RA治疗组,肾组织ACE活性和ANGⅡ浓度显著低于肾病对照组(P＜0.01)。结论:AT₁RA和ACEI在肾病综合征进行性肾损伤中,具有相似的肾脏保护作用,这种作用可能与抑制肾脏局部的ANGⅡ有关。     

抑制大鼠动脉损伤后早期中膜平滑肌细胞增殖可降低内膜肥厚

目的:探讨早期中膜平滑肌细胞增殖与内膜肥厚的关系。方法:球囊导管损伤大鼠动脉后,在不同时期投予血管紧张素转换酶抑制剂(ACEI)(temocapril-HCl,10mg·kg^-1·d^-1),观察平滑肌细胞BrdU(5-溴脱氧尿嘧啶尿苷)标记率和内膜面积。结果:损伤后动脉中膜平滑肌BrdU阳性细胞出现于术后24h,BrdU标记率呈双峰期变化,第1期在1-3d,峰值在2d为5.3%,第2期在3-7d,峰值在5d为2.7%。在第1个增殖期投予temocapril显著抑制第2个增殖期的BrdU标记率(0.05±0.02)%,对照组为(4.50±0.27)%(P＜0.01),同时也显著抑制了术后10d内膜面积的增加(10670.1μm²±7713.3μm²)(P＜0.01)。而仅在第2个增殖期投药,则不能抑制内膜面积的增加(83499.5μm²±31360.0μm²)(P＞0.05),其程度与未投药组相当。结论:球囊导管损伤后动脉中膜平滑肌细胞第1个增殖期是内膜形成所必需的。     

血管紧张素转换酶抑制剂对糖代谢的影响

血管紧张素转换酶抑制剂对糖代谢无不良影响，甚至可改善机体对胰岛素的敏感性、对代谢有益。它可通过改善机体对胰岛素的敏感性而诱发某些接受降血糖治疗的糖尿病患者发生低血糖。血管紧张素转换酶抑制剂可明显改善胰岛素抵抗。     

肾素-血管紧张素系统新成员：血管紧张素转换酶2

血管紧张素转换酶 2 (ACE2 )是血管紧张素转换酶 (ACE)的同系物 ,是肾素 血管紧张素系统的新成员。ACE2在肾素 血管紧张素系统中有着重要生理作用 ,其对高血压、心功能以及心电生理等有重要影响。     

血管紧张素转换酶基因与心血管疾病

血管紧张素Ｉ转换酶（ＡＣＥ）是肾素－血管紧张素系统（ＲＡＳ）的一个关键酶,为含锌的金属水解酶,ＡＣＥ基因多态性与血循环ＡＣＥ水平密切相关,ＡＣＥ基因可能是ＲＡＳ中与心血管疾病相关的最主要基因之一。ＡＣＥ基因Ｉ／Ｄ多态可能是高血压、冠心病、心肌病、等多种心血管疾病发病的独立危险因素。     

血管紧张素转换酶2与心血管疾病研究进展

血管紧张素转换酶2(ACE2)是SARS病毒(SARS-CoV)、新型冠状病毒(SARS-CoV-2)感染机体的主要受体,也是肾素-血管紧张素-醛固酮系统的主要成员之一。ACE2对多种心血管疾病具有保护作用,SARS-CoV-2可以降低机体ACE2的表达,这可能是新型冠状病毒肺炎(COVID-19)后期产生心血管并发症的原因之一。本文总结了ACE2在多种心血管疾病发病过程中的作用及其机制,希望为新型冠状病毒肺炎(COVID-19)的治疗提供新的思路。     

心肌梗塞患者血管紧张素转换酶基因缺失多态性分析

血管紧张素转换酶（ＡＣＥ）基因的多态性被认为与血浆ＡＣＥ浓度有关，同时也是欧洲人群心肌梗塞的独立的危险因子，尤其是那些一般被认为是心肌梗塞低危者。作者应用ＡＣＥ基因内含于１６多态区两侧的序列作为引物，用多聚酶链反应方法来检测ＡＣＥ基因多态性，对中国人中４０例心肌梗塞患者和４０例非冠心病患者进行了比较，结果表明心肌梗塞患者中ＤＤ基因型发生率（５０％）明显高于对照组（２０％）．在中国人中ＡＣＥ／ＤＤ基因型可能是心肌梗塞的重要危险因子。     

增强型体外反搏对犬急性心肌缺血时血管紧张素转换酶的影响

目的：探讨增强型体外反搏（ＥＥＣＰ）对我急性心肌缺血犬循环及局部组织中血管张素转换酶（ＡＣＥ）的影响。方法：结扎犬冠脉 左前降支造成急性心肌缺血模型,用紫外分光光度法测徨及局部组织ＡＣＥ活性。结果：急性心肌缺血时循环ＡＣＥ持续上升,１６５min时,上升幅度趋于平缓,经反搏治疗后６０min,未见对ＡＣＥ有影响,１２０min时ＡＣ Ｅ睛降,但仍高于下沉水平。局部ＡＣＥ在缺血时均被激活,反搏１２０min后,各组织Ａ     

Effects of angiotensin-converting enzyme inhibition on renal sodium handling after furosemide injection

Summary The goal of this study was to quantitate the effect of angiotensin-converting enzyme inhibition on renal sodium handling after furosemide injection. The study was carried out on low and normal salt intake to assess potential interaction with salt balance. Eighteen healthy normotensive volunteers were examined in a double placebo-controlled parallel group design. Subjects were randomly put on either low-salt (20 mmol/day) or normal-salt (110 mmol/day) diet. In either arm of the diet volunteers were first treated orally with placebo for 1 week and subsequently with 2.5 mg/day of the angiotensin-converting enzyme inhibitor cilazapril for another 1 week. Cumulative 24-h urinary sodium excretion was measured on the 6th day of the respective week after sham injection and on the 7th day after injection of 40 mg furosemide. Compared to pretreatment with placebo, pretreatment with cilazapril resulted in a higher cumulative sodium excretion after furosemide injection (day 7) than after the sham injection (day 6) on both salt intakes. The difference in natriuresis (cilazapril versus placebo) was evident 2 and 3 h after injection of furosemide. Neither the time of onset nor the magnitude of antinatriuresis were affected by cilazapril. Following furosemide angiotensin II increased significantly even after cilazapril pretreatment. Cilazapril tended to reduce urinary furosemide excretion. At any given urinary furosemide concentration, the increment in urinary sodium excretion was significantly greater with cilazapril irrespective of salt intake. The study shows that (a) cilazapril increases furosemide-induced natriuresis irrespective of salt intake, (b) antinatriuresis is not affected by cilazapril, and (c) angiotensin II levels rise after furosemide on cilazapril in therapeutic doses.Abbreviation ACE angiotensin-converting enzyme     

Effects of the new angiotensin-converting enzyme inhibitor,ramipril, in patients with essential hypertension

Summary The antihypertensive and hormonal effects of the new angiotensin-converting enzyme (ACE) inhibitor, ramipril, were assessed by means of a single-blind trial in ten unselected patients with mild-to-moderate essential hypertension. After a 2-week period on placebo, 5 mg ramipril was administered once daily for 2 weeks. Blood pressure returned to normal in five patients and decreased in the remaining patients, without significant changes in heart rate or orthostatic hypotension. A fall in blood pressure was apparent within 1–2 h of the first dose; the maximum decrease was reached at 4–6 h and a fall in pressure was still detectable after 24 h. At 24 h post dose angiotensin-converting enzyme activity was suppressed to 40% of the baseline. Blood pressures for the 10 h interval post dosing showed smooth through-the-day control with minimal peak/trough difference in lowering effect. The magnitude of the blood pressure decrement achieved with the inhibitor did not correlate with baseline renin levels or the rise in renin following treatment. No side-effects were noted during the 2-week observation period. The study demonstrates that ramipril, given in a once-daily regimen over a period of 2 weeks, is well tolerated and provides smooth and effective blood pressure control throughout the 24-h interval between doses.Abbreviations ACE angiotensin converting enzyme - PRA plasma renin activity     

血管紧张素转换酶固相化方法的选择

分别采用琼脂包埋法、卵清包埋法、海藻酸钙包埋法、明胶-戊二醛包埋法、溴化氰活化连接法和苯甲磺酰氯结合方法对血管紧张素转换酶进行固相化研究,发现苯甲磺酰氯结合法用于血管紧张素转换酶固相化效果最好。此实验是在低水活度条件下,利用苯甲磺酰氯在丙酮和吡啶存在的条件下活化Sepharose CL-4B凝胶侧链基团上的羟基,形成具有高反应活性的苯甲磺酰基团,在pH7.8的0.2mol/L HEPES-HCl缓冲系统中,4℃反应12h,将酶与凝胶连接在一起。25mg ACE与5g活化琼脂糖凝胶在这种条件下反应,所得固相酶活力为10.86U/mg,蛋白固相率达到66%,酶活力固相率为53.3%。固相酶4℃保存3个月,活力剩余80%,20℃保存1个月酶活残留61%。同样条件下,溶液酶活力分别只剩余62%和19%,由此可见血管紧张素转换酶经固相化后稳定性明显提高。     

Performance at altitude and angiotensin I-converting enzyme genotype

The insertion (I) rather than deletion (D) variant of the human angiotensin-converting enzyme (ACE) gene is associated with both lower tissue ACE activity and elite performance at high altitude. We examined whether the onset of acute mountain sickness (AMS), and further performance on reaching the summit of Mt. Blanc are influenced by the ACE I/D polymorphism. Two hundred and eighty-four climbers (235 males, [37.0 (11.0 years], (86 DD, 142 ID, 56 II)) had assessment of their AMS status upon arrival to the Gouter hut (3,807 m) on day 1, and again on day 2 after an attempted ascent to the summit of Mt. Blanc (4,807 m). Success in reaching the summit was genotype dependent (87.7% of DD, 94.9% of ID and 100% of II individuals; P=0.048); I allele frequency for those reaching the summit was 0.47 compared to 0.21 for those who did not (P=0.01). The onset of AMS on day 1 appeared to be dependent on genotype (P=0.003), but with those heterozygous being less affected. ACE genotype was not associated either with AMS onset or severity on day 2. Thus, ACE I/D genotype is associated with successful high altitude ascent in this prospective study—an association not explicable by genotype-dependence of AMS onset or severity. Values are given as mean (SD) unless otherwise stated.     

血小板源生长因子和血管紧张素Ⅱ对血管平滑肌细胞中细胞周期相关基因表达的影响

目的:观察血小板源生长因子-BB(PDGF-BB)和血管紧张素Ⅱ(AngⅡ)对血管平滑肌细胞(VSMC)中细胞周期相关基因表达影响的异同。方法:第4-6代培养的大鼠胸主动脉平滑肌细胞,AngⅡ10^-6mol/L和PDGF-BB20μg/L刺激静止后的VSMC,24h收集细胞。用TR1zol试剂提取VSMC中的总RNA,然后用DNA酶纯化总RNA,按DNA芯片试剂盒(Atlas^TMHuman CellCycle Arrays,Clontech公司)的步骤用标记探针,并纯化探针,然后杂交、显影,检测细胞周期相关基因的表达。结果:PDGF-BB刺激组cyclinD3mRNA、cyclinG1mRNA、p57mRNA和p16mRNA相对光密度值明显高于AngⅡ组,前者分别为后者的2.67倍、1.59倍、2.47倍、1.78倍,AngⅡ组E2F-3mRNA和DP2mRNA表达量分别低于PDGF-BB组40.34%和54.07%;而p15mRNA、p19mRNA、E2F-1mRNA、E2F-5mRNA以及N-mycmRNA仅在PDGF-BB刺激组表达;p53结合蛋白mRNA相对A值在AngⅡ组高,为PDGF-BB组的1.94倍;PCNAmRNA、c-myc结合蛋白mRNA、p53依赖性细胞生长因子mRNA、cyclinCmRNA、cyclinB1mRNA、E2F-3mRNA表达在PDGF-BB组和AngⅡ组中接近。结论:在PDGF-BB和AngⅡ诱导的VSMC增殖或肥厚过程中,细胞周期相关基因的表达是不完全相同的。     

运动与苯那普利联合治疗对胰岛素抵抗的影响

目的：研究运动训练与血管紧张素转换酶抑制剂（ACEI）苯那普利联合或单独治疗对高脂饮食大鼠胰岛素抵抗（IR）的影响。方法：雄性Wistar大鼠36只，随机分为6组：正确对照（NC）组，正常运动（NE）组、高脂饮食（HF）组、高脂运动（EHF）组、高脂苯那普利（BHF）组和高脂、运动、苯那普利联合治疗（CHF）组。以葡萄糖-胰岛素耐量试验（G-InsTT）检测胰岛素敏感性，同时检测空腹、餐后血糖、血清FFA及空腹胰岛素浓度（FIns）。结果：HF组大鼠Fins水平明显高于NC组，G-InsTT中K值明显低于NC组（P<0.01）；而EHF组、BHF组、CHF组FIns水平均低于HF组，G-InsTT中K值明显高于HF组（P<0.01），尤以CHF组效果更显著。结论：长期高脂饮食导致的IR的发生，运动训练与苯那普利均明显减轻IR，二者联合应用优于单一治疗。     

血清血管紧张素转换酶和血管紧张素原水平与妊娠高血压综合征的相关性及其危险因素

目的 探讨血清中血管紧张素转换酶(ACE)和血管紧张素原 (AGT)与妊娠期高血压综合征（HDCP）的相关性及HDCP发病的危险因素。 方法 选择135例妊娠高血压患者（HDCP组）和100例正常孕妇（CK组）,用ELISA法检测各组的血清ACE、AGT水平,并进行相关性分析;抽取两组孕产妇的年龄、怀孕天数、孕前体质量指数（BMI）、产次、产检次数、高血压糖尿病家族史、文化程度等一般资料,对孕产妇患HDCP的危险因素进行单因素分析,将单因素回归分析中有统计学意义的因素进行多因素 Logistic 回归分析。 结果 HDCP组血清ACE水平（90.49±47.65）μg/L明显高于CK组（58.72±27.58）μg/L,P<0.05,差异有统计学意义;HDCP组血清AGT水平（64.57±19.71）μg/L高于CK组（58.22±18.64）μg/L,P>0.05,差异无统计学意义;单因素分析结果显示,年龄、BMI、高血压、糖尿病家族史、ACE水平是孕产妇患HDCP的危险因素（P<0.05）,怀孕天数、产次、产检次数、文化程度比较差异无统计学意义（P>0.05）;多因素分析显示：年龄、BMI、高血压糖尿病史、ACE水平是妊娠性高血压的危险因素。 结论 ACE水平与HDCP有关,AGT水平与HDCP无关;年龄大、BMI值高、有高血压糖尿病史者,ACE水平增高发生妊娠高血压综合征的风险增加。