新型冠状病毒肺炎与血管紧张素转化酶2的研究现状

自2019年底起，新型冠状病毒肺炎（Coronavirus disease 2019，COVID-19）病例席卷全球。该病毒为β属冠状病毒，基因特征与严重急性呼吸综合征冠状病毒（Severe Acute Respiratory Syndrome Coronavirus，SARS-CoV）有较高相似性，被命名为2019新型冠状病毒（2019 Novel Coronavirus，2019-nCoV）或严重急性呼吸综合征冠状病毒-2（SARS-CoV-2），主要通过棘突蛋白介导与宿主血管紧张素转化酶2（angiotensin-converting enzyme 2，ACE2）受体结合侵犯人体。ACE2与COVID-19感染密切相关，既是SARS-CoV-2感染人体的关键靶点，ACE2表达多寡也是影响COVID-19患者疾病严重程度和死亡率的重要因素。因此靶向ACE2和肾素-血管紧张素系统（renin-angiotensin system，RAS）的诸多上市药物和在研药物，如血管紧张素转化酶抑制剂（angiotensin-converting enzyme inhibitor，ACEI）、血管紧张素受体拮抗剂（angiotensin receptor blocker，ARB）、重组人ACE2、Ⅱ型跨膜丝氨酸蛋白酶（type II transmembrane serine proteases，TMSPSS2）抑制剂、特异性中和抗体等都有可能成为治疗COVID-19的可行策略。此外，依据现有证据并不建议合并高血压的轻症COVID-19确诊病例或疑似病例轻易停用ACEI/ARB，以免造成血压波动。     

血管紧张素转化酶2受体及ACEI或ARB类药物与新型冠状病毒肺炎的相关性

患有高血压的新型冠状病毒肺炎(COVID-19)患者是否可以使用血管紧张素转化酶抑制剂(ACEI)或血管紧张素2受体拮抗剂(ARB)类药物引起关注。该文对COVID-19与血管紧张素转化酶2(ACE2),以及ACEI或ARB类药物与ACE2的相关性进行探讨,结合目前已知证据提出ACEI或ARB类药物与COVID-19可能的相关性。建议目前已使用ACEI或ARB类药物高血压患者不需停药,而未使用者应谨慎选用。     

血管紧张素转换酶抑制剂/血管紧张素受体拮抗剂在新型冠状病毒肺炎疫情防控中的应用分析

根据《中国心血管病报告》,中国现患心血管病人数约2.9亿,而大量循证医学证据证实了血管紧张素转换酶抑制剂(ACEI)或血管紧张素受体拮抗剂(ARB)治疗心血管等疾病的价值.ACEI/ARB是肾素-血管紧张素-醛固酮系统(RAAS)的阻滞剂,可上调血管紧张素转换酶2(ACE2)表达水平.而ACE2是新型冠状病毒肺炎(CO...     

不同方法治疗早期糖尿病肾病的临床研究

目的探讨血管紧张素转换酶抑制剂（ACEI）联用血管紧张素Ⅱ型受体（AT-Ⅱ）拮抗剂治疗早期糖尿病肾病的合理性。方法60例2型糖尿病并发的早期糖尿病肾病患者，随机分为贝那普利组（n=20）、厄贝沙坦组（n=20）及两药联用组（n=20）治疗18周，治疗前后对平均动脉压（MAP）、尿白蛋白排泄率（UAER）、内生肌酐清除率（OD）、血清肌酐（Scr）、血清尿素氮（BUN）、空腹血糖（FBG）、餐后2h血糖（2hBG）、糖化血红蛋白（HbA1c）、血脂分析、血清钾进行比较。结果贝那普利组UAER治疗后比治疗前下降了33．9％（t=3．278，P=0．004），厄贝沙坦组下降了36．2％（t=4．234，P〈0．01），两药联用组（贝那普利＋厄贝沙坦）下降了60．9％（t=5．754，P〈0．01），两单药组间下降幅度无明显差异（P〉0．05），联用组较单药组下降幅度总体增加26．1％。结论ACIEI与AT1拮抗剂联合应用治疗早期糖尿病肾病有一定的临床价值。     

新型冠状病毒肺炎感染两性差别研究进展

新型冠状病毒肺炎由于其极强的传染力目前仍在全球范围内广泛流行,对人们的生命健康造成了极大威胁.然而,通过查阅研究既往文献资料发现,在感染率、危重状况和死亡率上存在性别上的差异.比起女性,男性在新冠肺炎中更容易被感染且病情更严重死亡率更高.首先,性别会对肾素-血管紧张素系统(RAS系统)中的关键成分血管紧张素转换酶-2的...     

血管紧张素转换酶2在新型冠状病毒感染及治疗中的作用概述

摘要：血管紧张素转换酶2(ACE2)是肾素-血管紧张素系统(RAS)重要的组成部分,能够下调RAS,具有抗炎、抗纤维化等作用。同时ACE2还是新型冠状病毒(SARS-CoV-2)的受体,与SARS-CoV-2感染及感染后的临床表现密切相关。血管紧张素转化酶抑制药/血管紧张素Ⅱ受体阻断药(ACEI/ARB)在SARS-CoV-2感染中的作用,目前研究尚有争议。本文对ACE2及ACEI/ARB类药物在SARS-CoV-2感染中的作用作一综述。基于目前的研究证据,建议感染前已使用ACEI/ARB类药物的新型冠状病毒肺炎(COVID-19)患者继续用药,但目前尚不建议将ACEI/ARB类药物用于COVID-19患者的治疗。     

新型冠状病毒感染疫情中ACEI的争议：下结论还为时尚早

近期,新型冠状病毒感染合并高血压的患者,是否应停用血管紧张素转换酶抑制剂(ACEI)引起了争议。血管紧张素转换酶2(ACE2)是血管紧张素转换酶(ACE)的同源物,两者在血压调控和肺损伤中发挥重要作用。ACE2也是新型冠状病毒感染呼吸道上皮细胞的作用靶点。目前,关于ACEI对新型冠状病毒感染患者的ACE2调控效应出现了不同理论,ACEI/ARB对ACE2的调控效应尚无定论。此外,目前研究结果多数来自于动物实验,尚无临床数据。由于证据有限,因此使用ACEI/ARB类降压药的新型冠状病毒感染患者暂不必换药。     

抗新型冠状病毒中和抗体研究进展

自首次报道以来,新型冠状病毒（2019 novel coronavirus,2019-nCoV）引起的新型冠状病毒肺炎已迅速在全球传播。2019-nCoV感染可引起严重肺炎,危及患者生命,目前尚无特效药物。2019-nCoV刺突蛋白及其受体血管紧张素转化酶2的结构已获得解析,为药物的开发提供了基础。通过人外周血单B细胞抗体筛选技术及其他抗体筛选技术,已获得多种针对2019-nCoV的中和抗体。抗体药物的开发为新型冠状病毒肺炎的预防和治疗提供了新的选择。此文简要综述抗2019-nCoV抗体类药物的研究开发。     

慢性心力衰竭住院患者的合并症对药物治疗影响的研究

目的:了解慢性心力衰竭患者的并发症是否对血管紧张素转换酶抑制剂(ACEI)、β-受体阻滞剂、血管紧张素Ⅱ受体拮抗剂(ARB)等药物的治疗产生影响.方法:选取1973年7月-2007年7月间的慢性心力衰竭住院患者,进行回顾性调查,包括年龄、性别、病因、合并症、电解质、心功能以及ACEI、β-受体阻滞剂、ARB等药物的应用情况.根据年代分为A(1973～)、B(1980～)、C(1990～)、D(2000～2007)共4组.结果:入选6602例次,男3 325例次(50.4%),女3277例次(49.6%).合并高血压、糖尿病、脑血管病、肾功能不全、贫血在4组中差异有统计学意义.ACEI、ARB和β-受体阻滞剂在合并高血压、糖尿病、慢性肾功能不全、贫血等患者中的应用比例均高于无合并症者,并于最近年代中的应用比例增加.结论:在某种程度上,高血压、糖尿病、脑血管病、慢性肾功能不全、贫血等合并症的存在使慢性心力衰竭患者使用ACEI、ARB和β-受体阻滞剂机会增加.     

Current treatment of hypertension in patients with coronary artery disease recommended by different guidelines

Introduction: It is important to know how to treat hypertension in patients with coronary artery disease (CAD). The reason for the review was to update this treatment and to discuss the 2015 American Heart Association/American College of Cardiology/American Society of Hypertension 2015 guidelines of treatment of hypertension in patients with CAD.

Areas covered: Studies between 1968 and 2015 were reviewed on treatment of hypertension in patients with CAD using a Medline search, and studies between 1977 and 2015 were reported. Hypertension should be treated with beta blockers and ACE inhibitors or angiotensin receptor blockers (ARBs). Long-acting nitrates are effective antianginal and anti-ischemic drugs. Calcium-channel blockers (CCBs) may be added if angina persists despite beta blockers and long-acting nitrates. The 2015 guidelines recommend that the blood pressure should be < 140/90 mm Hg in patients aged ≤ 80 years and the systolic blood pressure < 150 mm Hg if they are ≥ 80 years.

Expert opinion: Hypertension in patients with CAD should be treated with beta blockers and ACE inhibitors or ARBs. Long-acting nitrates are effective antianginal and anti-ischemic drugs. CCBs may be added if angina persists despite beta blockers and long-acting nitrates. The blood pressure should be < 140/90 mm Hg in patients aged < 80 years and the systolic blood pressure < 150 mm Hg if they are ≥ 80 years.     

Delayed Initiation of Remdesivir in a COVID-19-Positive Patient

We present a case of late initiation of remdesivir antiviral therapy in the successful treatment of a patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a mixed medical intensive care unit of a community teaching hospital. A previously healthy 40-year-old man was admitted to the hospital 3 days after the onset of coronavirus disease 2019 (COVID-19) symptoms including dry cough, fever, and shortness of breath progressing to intubation and increased mechanical ventilator support. A request for compassionate use remdesivir was submitted on the same hospital day as the positive COVID-19 polymerase chain reaction result. Supportive measures, in addition to a 5-day course of hydroxychloroquine, were maintained until remdesivir could be supplied on day 9 of hospitalization, 13 days after symptom onset. Sixty hours after initiating remdesivir, the patient was successfully extubated and able to transition to room air within 24 hours of extubation. Late initiation of remdesivir may be effective in treating SARS-CoV-2, unlike antivirals utilized for different disease states, such as oseltamivir, that are most effective when started as soon as possible following symptom onset. Urgent action is needed by regulatory agencies to work with drug manufacturers to expedite the study and approval of investigational agents targeting SARS-CoV-2 as well as to meet manufacturing demands.     

肾素-血管紧张素系统在COVID-19中作用及药物干预

COVID-19的发病特征为发热、干咳、乏力,严重者可进展为急性呼吸窘迫综合征(ARDS)等,甚至危及生命。SARS-CoV-2可通过血管紧张素转化酶2(ACE2)入侵细胞并导致ACE2表达下调。ACE2表达下调会导致肾素-血管紧张素系统(RAS)的失衡,从而引起后续病理状态发生,RAS在ARDS中也发挥重要的作用。本文总结了RAS系统在COVID-19发病过程中可能存在的作用,以及基于RAS对于COVID-19的治疗可能,为优化治疗及后续研究提供参考。     

Different effects of perindopril and enalapril on monocyte cytokine release in coronary artery disease patients with normal blood pressure

BackgroundFavorable effects of angiotensin-converting enzyme (ACE) inhibitor treatment on the incidence of cardiovascular and cerebrovascular mortality and morbidity are not limited to patients with elevated blood pressure. As suggested by our previous results, the physicochemical and pharmacokinetic differences between drugs may markedly contribute to the strength of pleiotropic effects of ACE inhibitors.MethodsThe present study was aimed at comparing the effects of serum- and tissue-type ACE inhibitors on monocyte release of proinflammatory cytokines in normotensive patients with stable coronary artery disease. The participants were randomized to 90-day treatment with enalapril (20 mg daily, n = 29), perindopril (4 mg daily, n = 27) or placebo (n = 28). Plasma levels of lipids, glucose, insulin and high sensitivity C-reactive protein (hsCRP), as well as monocyte release of proinflammatory cytokines were determined before and after 30 days of therapy, and at the end of the treatment.ResultsLipopolysaccharide-stimulated monocytes from normotensive patients with stable coronary artery disease released significantly more TNF-α, interleukin-1β and monocyte chemoattractant protein-1 in comparison with monocytes from 23 matched control subjects. Their baseline hsCRP levels were also higher. Perindopril reversed the disease-induced changes in cytokine release and reduced plasma hsCRP, while the effect of enalapril was much more limited. The effect on both drugs on cytokine release was stronger in insulin-resistant than insulin-sensitive subjects.ConclusionsOur results indicate that perindopril is superior to enalapril in producing monocyte-suppressing and systemic antiinflammatory effects in normotensive patients with coronary artery disease. This action may contribute to the clinical effectiveness of tissue ACE inhibitors in the therapy of atherosclerosis-related disorders, particularly in insulin-resistant subjects.     

新型冠状病毒肺炎患者继发感染的危险因素分析

摘要：目的　探讨新型冠状病毒肺炎（COVID-19）患者继发细菌感染的危险因素。方法　回顾性分析天津市海河医院收治的136例COVID-19患者的临床资料,根据临床诊断结果分为继发细菌性肺炎（继发感染组,44例）和非继发感染组（92例）。比较2组患者临床特征、治疗、疾病转归等差异,Logistic回归分析患者继发感染的危险因素。结果　继发感染组患者年龄、合并基础疾病比例高于非继发感染组（P＜0.01）,入院的氧合指数（OI）＜400 mmHg、高热（体温>39 ℃）、重症、合并急性呼吸窘迫综合征（ARDS）、低蛋白血症、心功能不全比例也均高于非继发感染组,接受机械通气治疗、有创操作、激素治疗比例及住院时间均高于非继发感染组（P＜0.05）。Logistics 回归分析显示,合并基础疾病（OR=4.613,95%CI：1.756~12.118）、激素治疗（OR=2.403,95%CI：1.012~6.422）、入院OI＜400 mmHg（OR=6.534,95%CI：2.064~20.691）、低蛋白血症（OR=12.949,95%CI：3.284~51.067）是继发细菌感染的独立危险因素。结论　COVID-19继发感染与患者入院氧合指数低于400 mmHg、低蛋白血症、激素治疗、基础疾病关系密切,临床尽早干预可预防患者继发感染,有利于改善预后。     

Lymphocyte-suppressing action of angiotensin-converting enzyme inhibitors in coronary artery disease patients with normal blood pressure

The clinical effectiveness of angiotensin-converting enzyme (ACE) in the prevention and treatment of cardiovascular disorders partially results from its anti-inflammatory action. No previous study has investigated the effect of any ACE inhibitor on lymphocyte cytokine release. In this study, we compared the effects of serum- and tissue-type angiotensin-converting enzyme inhibitors on systemic inflammation and lymphocyte secretory function in normotensive patients with stable coronary artery disease. The study included 134 patients with coronary artery disease who were randomized into one of three groups and treated with enalapril (20 mg/d, n = 47), perindopril (4 mg/d, n = 45) or placebo (n = 42), respectively. The control group included 40 age-, sex- and weight-matched healthy subjects. The plasma lipid profile, glucose metabolism markers, hsCRP and lymphocyte cytokine release were examined at the beginning of the study and after 30 and 90 days of treatment. Phytohemagglutinin-stimulated T cells released significantly more interleukin-2, interferon-γ and TNFα than the lymphocytes of control subjects. Neither enalapril nor perindopril treatment was associated with any significant changes in blood pressure. Perindopril treatment inhibited lymphocyte cytokine release and systemic inflammation, while the effect of enalapril was insignificant. Perindopril, and, to a lesser extent, enalapril, strongly reduced lymphocyte cytokine release in insulin-resistant but not insulin-sensitive subjects. Our results indicate that perindopril is superior to enalapril in producing lymphocyte-suppressing and systemic anti-inflammatory effects in normotensive coronary artery disease patients. These effects may contribute to a reduction in the vascular risk of this group of patients, particularly in those subjects who are resistant to insulin, when these patients are treated with tissue-type angiotensin-converting enzyme inhibitors.     

基于数据库挖掘以血管紧张素转化酶2为靶点治疗新型冠状病毒肺炎的潜在中药成分

目的 利用中药数据库寻找抑制血管紧张素转化酶2（ACE2）治疗新型冠状病毒肺炎（COVID-19）的潜在中药成分。方法 借助SYMMAP、TCMID、ETCM数据库,以ACE2为搜索词,筛选中药成分及中药材,利用GCBI平台来筛选与靶点相关的炎症因子,得到相关疾病及核心网络图。将ACE2输入到STITCH数据库中,查询阳性对照药物。运用Sybyl（2.0）软件处理受体,中药成分与阳性对照药均和ACE2（1R42）及新型冠状病毒（SARS-CoV-2）3CL pro（6LU7）进行对接分析。应用Swiss ADME平台为对接结果较好的中药成分和阳性对照药构建雷达图。结果 从数据库中找到7种具有抑制SARS-CoV-2潜在活性的中药成分和相关中药材。网络分析图中连接基因数最多的是CXCR4基因,它涉及到细胞因子-细胞因子受体相互作用、趋化因子信号通路可能是发挥治疗COVID-19的潜在机制。分子对接的结果表明,2'',4'',3,4-四羟基查尔酮、葛根素与SARS-CoV-2相关蛋白结合最好。结论 2'',4'',3,4-四羟基查尔酮等中药成分可能是治疗COVID-19的潜在成分。     

New advances in the pharmacological management of chronic heart failure

The management of heart failure has evolved in parallel with advances in the understanding of the disease process. Inotropes and diuretics are used to combat pump failure and fluid overload. While no convincing data has emerged regarding the long-term safety of inotropes, new exciting data concerning the role of diuretics, especially aldactone, has led to a renewed interest in this class of drug therapy. Angiotensin converting enzyme inhibitors (ACE inhibitors) were noted to not only affect symptomatology but also decrease mortality by interfering with the renin-angiotensin-aldosterone system. Recent research has focused on more complete blockade of the renin-angiotensin system than that achieved with ACE inhibitors alone with the addition of direct angiotensin II receptor blockers. This new class of drugs may become not only a reasonable alternative to ACE inhibitors in patients intolerant of the drug but also a possible addition to ACE inhibitors in the battle to prevent progression of remodelling and disease. β-blockers are the most exciting new class of drugs used to combat heart failure. They appear not only to combat the remodelling process that occurs in the progression of disease but also other pathological events such as apoptosis and cellular oxidation. New medical therapies currently being investigated include novel agents such as endothelin antagonists, natriuretic peptides, vasopressin antagonists and anticytokine agents - all part of a new era in drug management of heart failure that has evolved with continued advances in the understanding of chronic heart failure (CHF).     

浅谈天津地区新型冠状病毒肺炎救治体会

摘要：新型冠状病毒肺炎（COVID-19）是一种新型传染性疾病,尽管我国在临床诊治和防控上已取得了很大进 步,但COVID-19具有独特的临床症状和影像学表现,其病毒亦具有特有的生物学特征,临床救治仍面临许多挑战, 需要医学专家们在救治工作中不断认知和积累经验,从而进一步规范临床诊治方案。本文就天津市收治的136例确 诊病例的总体救治情况及重症病例的早期诊断和预警、抗感染策略、危重患者管理等方面进行总结,以更好地指导 临床实践。