评价在β受体阻滞剂治疗慢性充血性心力衰竭中脑利钠肽检测的意义

目的评价在β受体阻滞剂治疗慢性充血性心力衰竭中脑利钠肽检测意义。方法选取2011年2月至2013年12月期间我院收治的慢性充血性心力衰竭患者120例,将120例患者按照治疗方式分为三组,基础组40例患者,美托洛尔组40例患者,卡维地洛组40例患者。基础组患者给予血管紧张素转换酶抑制剂、利尿剂、地高辛等慢性充血性心力衰竭的常规临床方式进行治疗;美托洛尔组患者在基础组治疗的基础上加用美托洛尔进行治疗;卡维地洛组患者在基础组治疗的基础上加用卡维地洛进行治疗。结果三组患者治疗后的ANP和BNP水平均较治疗前有显著降低,组内比较差异具有统计学意义(P<0.05);其中BNP下降的幅度要远远高于ANP下降的幅度,比较差异具有统计学意义(P<0.05)。美托乐儿组与卡维地洛组ANP和BNP水平下降幅度显著高于基础组,比较差异具有统计学意义(P>0.05),美托乐儿组与卡维地洛组之间的差异不具有统计学意义(P>0.05)。对于EF值较低的患者来说,如果其能够耐受β受体阻滞剂的治疗,则其获益会更大。结论脑利钠肽检测不仅能够诊断心功能不全,还可以反映出慢性充血性心力衰竭的病情严重程度和预后,同时还能够对β受体阻滞剂的治疗反应进行准确的评价。     

不同β-受体阻滞剂对心力衰竭患者β-受体与β1-受体基因表达干预性研究

目的 研究心力衰竭患者外周血淋巴细胞β-受体（β-AR）密度和β1-受体基因（β1-AR mRNA）表达水平的变化规律，探讨不同β-受体阻滞剂对β-AR和β1-AR mRNA表达水平的影响。方法 将104例心衰患者随机分为非β-受体阻滞剂治疗组（35例）、美托洛尔治疗组（34例）和卡维地洛治疗组（35例），2个月后复测β-AR和β1-AR mRNA表达水平。结果 心衰组β-AR密度和β1-AR mRNA表达水平较正常人明显下降（P〈0．01），心功能Ⅳ级患者下降更明显（P〈0．01）。冠心病与扩张型心肌病两组之间差异无显著意义（P〉0．05）。治疗后，美托洛尔治疗组β-AR密度和β1-AR mRNA表达水平明显高于卡维地洛治疗组和非β-受体阻滞剂治疗组（P〈0．01），卡维地洛治疗组与非β-受体阻滞剂治疗组差异无显著意义。结论 心衰时外周血淋巴细胞β-AR密度和β1-AR mRNA表达水平下调、下调幅度与心衰严重程度有关，与病因无关。应用美托洛尔能明显上调β-AR密度和β1-AR mRNA表达水平，卡维地洛则无此作用。     

依那普利联合卡维地洛对慢性心力衰竭患者心功能与神经内分泌功能及血管内皮功能的影响

目的 探讨依那普利联合卡维地洛治疗慢性心力衰竭(CHF)的临床效果.方法 选取2014年1月～2016年7月我院104例CHF患者,根据治疗方案分组,各52例.在常规治疗基础上,对照组给予依那普利治疗,观察组给予依那普利+卡维地洛治疗.对比两组治疗前后左室射血分数(LVEF)、内皮素(ET)及神经内分泌功能指标[醛固醇(ALD)、血管紧张素Ⅱ(ATⅡ)、肾素活性(PRA)]水平.结果 治疗前,两组LVEF、ET及PRA、ATⅡ、ALD水平差异无统计学意义(P＞0.05),经治疗,观察组LVEF高于对照组,ET及PRA、ATⅡ、ALD低于对照组,差异有统计学意义(P＜0.05).结论 依那普利联合卡维地洛治疗慢性心力衰竭,有利于改善患者心功能及内皮功能,且对神经内分泌功能调节作用显著.     

参附注射液对慢性心力衰竭患者NT-ProBNP水平及心功能的影响

目的:观察参附注射液对慢性心力衰竭患者血浆脑钠肽水平及心功能的影响.方法:将80例慢性心力衰竭(心衰)患者随机分为观察组和对照组,均予常规抗心衰治疗,观察组加用参附注射液,疗程2周.治疗前后用彩超测定心功能指标f左心室射血分数(LVEF)、左心室舒张末期内径(LVDd)],EUSA法和散射比浊法测定血浆N-末端脑钠肽前体(NT-proBNP)水平.结果:治疗后观察组总有效率明显高于对照组,心功能指标LVEF明显升高、LVDd明显下降,血浆NT-proBNP水平均明显下降(P<0.05);观察组血浆NT-proBNP与LVEF呈负相关(r=-0.72,P<0.05),与LVDd呈正相关(r=0.75,P<0.05).结论:参附注射液治疗慢性心衰效果确切,其主要作用机制可能与降低血浆NT-proBNP水平有关.     

生脉饮加ACEI及β-受体阻滞剂治疗慢性心力衰竭40例

目的观察生脉饮加血管紧张素转换酶抑制剂及β-受体阻滞剂在治疗慢性心力衰竭中对提高ACEI及β-受体阻滞剂达标率的效果。方法将80例慢性心力衰竭患者随机分为治疗组及对照组,各40例,治疗组在单纯西医治疗基础上加生脉饮口服液,对照组采用单纯西医常规治疗。结果治疗组达到目标剂量者ACEI为87.5%,β-受体阻滞剂为70%;对照组达到目标剂量者ACEI为70%,β-受体阻滞剂为50%。结论心衰治疗中加用生脉饮能够提高患者对ACEI及β-受体阻滞剂的耐受性,从而提高ACEI及β-受体阻滞剂在心衰治疗中达到目标剂量的比率。     

卡维地洛治疗慢性心力衰竭的临床疗效观察

慢性心力衰竭是心脏病的最终结局。也是心脏病患者死亡的主因。随着平均寿命的延长，心衰的发病率有逐年增高的趋势。近年来，β-受体阻滞剂在慢性心衰治疗中已发挥了币要的作用，而新一代的β-受体阻滞剂卡维地洛在治疗慢性心力衰竭的临床试验中被认为是一种非常有前途的药物。对2003年12月～2004年12月住院的慢性心衰患者应用卡维地洛和倍他乐克治疗进行对照观察。现报道如下：     

β受体阻滞剂治疗对慢性心力衰竭患者的影响研究

目的:分析β受体阻滞剂治疗对慢性心力衰竭患者的影响。方法:选取2019年1月～2020年3月某院收治的慢性心力衰竭患者126例,根据患者治疗方案的不同分为研究组(采用β受体阻滞剂治疗)与对照组(采用血管紧张素Ⅱ受体拮抗剂治疗)各63例,比较两组临床疗效、治疗前后心功能指标以及B型脑钠肽(BNP)的变化。结果:研究组总治疗有效率明显高于对照组(P0.05);两组治疗前CI、LVEF与BNP的比较差异无统计学意义(P0.05),研究组治疗后CI、LVEF明显高于对照组(P0.05),且治疗后BNP明显低于对照组患者(P0.05)。结论:β受体阻滞剂在慢性心力衰竭中的应用有助于改善患者的心功能状况,有助于提高患者的临床疗效。     

β-受体阻滞剂治疗心力衰竭的疗效观察

目的观察β受体阻滞剂治疗心力衰竭的临床疗效。方法将75例患者随机分为β-受体阻滞剂组和常规治疗组,β-受体阻滞剂组在常规抗心衰治疗的基础上给予β-受体阻滞剂;常规治疗组采用安慰剂加常规抗心衰治疗。结果β-受体阻滞剂治疗5年后再住院率和死亡率,心功能及超声指标与常规治疗组相比明显改善。结论β-受体阻滞剂可显著改善心力衰竭患者的远期预后。     

卡维地洛治疗慢性心衰的疗效及对血浆脑钠肽水平的影响

目的对比研究卡维地洛治疗慢性心衰的疗效及对患者血浆脑钠肽水平的影响。方法随机抽取2010年9月至2011年9月于我科就诊的慢性心力衰竭患者80例,随机均分为实验组及对照组各40例,对照组使用常规治疗,实验组在此基础上加用卡维地洛,所有患者治疗前及治疗结束后均进行心功能评级、心脏彩超检查和血浆BNP测试。结果治疗结束后,两组患者心功能均有改善,但实验组总有效率为92.5%,显著高于对照组,差异有统计学意义(P<0.05);实验组及对照组组内对比治疗后LVEDd、BNP均显著下降,LVEF均显著上升,差异均有统计学意义(P<0.05);实验组治疗后LVEDd、LVEF、BNP改变较对照组更为明显,组间差异具有统计学意义(P<0.05)。结论血浆脑钠肽可以作为治疗慢性心力衰竭的疗效判断指标;卡维地洛治疗慢性心力衰竭有着良好的疗效,能显著改善慢性心衰患者的心功能,降低BNP浓度,改善患者预后。     

黄芪注射液联合β受体阻滞剂对老年心力衰竭患者BNP、IL-1β、IL-6及TNF-α的影响

目的探讨黄芪注射液联合β受体阻滞剂对老年心力衰竭患者血清脑尿钠肽(BNP)、白细胞介素-1(IL-1β)、白细胞介素-6(IL-6)及肿瘤坏死因子(TNF-α)水平的影响。方法选取2013年4月~2015年4月杭州市余杭区第二人民医院心内科收治的78例心力衰竭患者,随机分为实验组和对照组,各39例,给予纠正电解质与酸碱平衡等常规治疗后,对照组患者采用口服β受体阻滞剂卡维地洛片的治疗方案,实验组患者则在对照组的基础上加用黄芪注射液。2组患者均治疗30 d,比较治疗前后2组患者血清中BNP、IL-1β、IL-6及TNF-α水平。结果治疗后2组患者血清IL-1β、IL-6、TNF-α及BNP水平与治疗前相比均降低(P<0.05);与对照组相比,实验组患者血清IL-1β、IL-6,TNF-α及BNP水平较低(P<0.05)。结论黄芪注射液联合β受体阻滞剂能明显改善老年心力衰竭患者体征,推测其机制可能与降低血清IL-1β、IL-6、TNF-α及BNP水平有关。     

Bradykinin-potentiating peptides and C-type natriuretic peptides from snake venom

Cloning of cDNAs encoding bradykinin-potentiating peptides (BPPs)-C-type natriuretic peptide (CNP) precursor or its homologue was performed for cDNA libraries of Bothrops jararaca (South American snake), Trimeresurus flavoviridis, Trimeresurus gramineus and Agkistrodon halys blomhoffi (Asian snakes), all belonging to Crotalinae subfamily. Each cDNA library was constructed from the venom glands of a single snake to preclude ambiguity by intraspecies variation in venom components. Thirteen positive clones derived from B. jararaca were divided into two types depending on restriction sites. Differences in the nucleotide sequence arise at three locations and two of them accompanied amino acid conversions. Despite the differences, both types of cDNA clones encode the BPP-CNP precursor of 256 amino acid residues. Sequence analysis demonstrated that cDNA clones from three Asian snakes encode homologues of the BPP-CNP precursor from B. jararaca. In a precursor polypeptide, a signal sequence (approximately 25 aa) at the N-terminus is followed by sequences of BPP or the analogue (5-13 aa) with flanking spacer sequences (indefinite number of aa), an intervening linker sequence (approximately 144 aa) with unidentified function, and a CNP sequence (22 aa) with a preceding processing signal sequence (10 aa). cDNA clones from A. halys blomhoffi encode two distinct peptides in place of BPP, and T. flavoviridis and T. gramineus were shown to have considerably different sequences in the BPP domain from those known as BPP sequences. The present results provide evidence for a wide distribution of the orthologous gene expressing a series of bioactive peptides among Crotalinae subfamily.     

Caffeine-induced diuresis and atrial natriuretic peptides.

After a single-blind, randomized, cross-over protocol using decaffeinated coffee in a control experiment, the effect of an oral 250-mg caffeine dose on plasma immunoreactive atrial natriuretic peptide (ANF) was assessed in eight healthy students who had been on a methylxanthine-free diet for 1 week. One to 2 h after caffeine ingestion, both systolic blood pressure (SBP) and diastolic BP (DBP) increased by 12 mm Hg while heart rate (HR) also tended to increase. An increase in diuresis and in urinary sodium, potassium, and osmol excretion was observed within 1 h. Decaffeinated coffee induced no change in any of these parameters. Plasma epinephrine (EPI) increased gradually from 16.6 +/- 3.2 pg/ml (mean +/- SEM) to 45.1 +/- 7.9 pg/ml within 2 h after caffeine ingestion, but did not change after decaffeinated coffee (p less than 0.001). Plasma norepinephrine (NE), renin activity (PRA), aldosterone, and vasopressin remained unchanged. Plasma ANF was measured by radioimmunoassay (RIA) using an extremely sensitive antiserum (Kd = 10(-12) M) after rapid and virtually complete (90-103%) extraction from plasma. In 0.2 ml plasma, the theoretical detection limit is 1.1 fmol/ml. Normal plasma ANF concentrations in supine subjects were 17.9 +/- 8.1 fmol/ml (mean +/- SD) and 11.0 +/- 3.3 fmol/ml in subjects in the upright position. Plasma ANF levels were not affected by coffee drinking. In conclusion, by using a new and sensitive assay for plasma ANF, we did not find that caffeine-induced diuresis is mediated by ANF.     

Endothelial actions of atrial and B-type natriuretic peptides

The cardiac hormone atrial natriuretic peptide (ANP) is critically involved in the maintenance of arterial blood pressure and intravascular volume homeostasis. Its cGMP-producing GC-A receptor is densely expressed in the microvascular endothelium of the lung and systemic circulation, but the functional relevance is controversial. Some studies reported that ANP stimulates endothelial cell permeability, whereas others described that the peptide attenuates endothelial barrier dysfunction provoked by inflammatory agents such as thrombin or histamine. Many studies in vitro addressed the effects of ANP on endothelial proliferation and migration. Again, both pro- and anti-angiogenic properties were described. To unravel the role of the endothelial actions of ANP in vivo, we inactivated the murine GC-A gene selectively in endothelial cells by homologous loxP/Cre-mediated recombination. Our studies in these mice indicate that ANP, via endothelial GC-A, increases endothelial albumin permeability in the microcirculation of the skin and skeletal muscle. This effect is critically involved in the endocrine hypovolaemic, hypotensive actions of the cardiac hormone. On the other hand the homologous GC-A-activating B-type NP (BNP), which is produced by cardiac myocytes and many other cell types in response to stressors such as hypoxia, possibly exerts more paracrine than endocrine actions. For instance, within the ischaemic skeletal muscle BNP released from activated satellite cells can improve the regeneration of neighbouring endothelia. This review will focus on recent advancements in our understanding of endothelial NP/GC-A signalling in the pulmonary versus systemic circulation. It will discuss possible mechanisms accounting for the discrepant observations made for the endothelial actions of this hormone-receptor system and distinguish between (patho)physiological and pharmacological actions. Lastly it will emphasize the potential therapeutical implications derived from the actions of NPs on endothelial permeability and regeneration.     

利尿排钠激素对眼内压的药理作用

青光眼可引起不可逆的视觉损害乃至失明。眼内压的异常升高是本病发展过程中的主因目前,唯一有效的治疗手段是降低眼内压。眼内压是由房水的生成及排出之平衡所调控的。一旦平衡失调(如房水排出减缓),即会引起高眼内压进而导致视网膜和视神经的损伤。除现有药物外,许多生物活性肽类分子(如利尿排钠激素)对眼内压的影响已引起许多学者的极大兴趣与关注。本文意在总结已发表的有关这类多肽以及相关化合物(如中性内肽酶抑制药)对眼内压的药理作用。     

Recent advances in natriuretic peptides in congestive heart failure

Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are secreted by the heart and play important roles in the compensation of congestive heart failure with their vasodilating, natriuretic, antiproliferative, lusitropic and neurohumoral-modulating properties. Based on these beneficial properties, exogenous BNP was developed as a new treatment for congestive heart failure and approved in the US for acute decompensated heart failure. New therapeutic strategies for heart failure that are currently being investigated include chronic subcutaneous BNP administration and intermittent BNP infusions. Furthermore, strategies combining exogenous BNP with an inhibitor of the BNP-degrading enzyme neutral endopeptidase could contribute to maximising the actions of BNP and reduce the amount of exogenous BNP needed.     

Recent advances in natriuretic peptides in congestive heart failure

Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are secreted by the heart and play important roles in the compensation of congestive heart failure with their vasodilating, natriuretic, antiproliferative, lusitropic and neurohumoral-modulating properties. Based on these beneficial properties, exogenous BNP was developed as a new treatment for congestive heart failure and approved in the US for acute decompensated heart failure. New therapeutic strategies for heart failure that are currently being investigated include chronic subcutaneous BNP administration and intermittent BNP infusions. Furthermore, strategies combining exogenous BNP with an inhibitor of the BNP-degrading enzyme neutral endopeptidase could contribute to maximising the actions of BNP and reduce the amount of exogenous BNP needed.     

钠尿肽的中枢调控功能研究进展

目的:作为存在于机体的一类重要肽类激素,钠尿肽家族成员主要包括心房钠尿肽(atrial natriuretic peptide,肽(dendroaspis natriuretic peptide, DNP)、心室钠尿肽(ventricle natriuretic peptide, Ve NP)和血管钠肽(vasonatrinoeptide,Va NP)等。此外,因与经典的钠尿肽成员结构相似,骨织素(osteocrin,OSTN)也被认为是钠尿肽家族的一员。钠尿肽家族成员结构相对保守,功能多样,除发挥利尿、利钠、扩张血管、降低血压等功能外,还与焦虑、抑郁、学习记忆等中枢神经行为调控密切相关。本文就钠尿肽家族成员结构特征、中枢调控功能及其机制研究进展作一综述。     

Acute actions of natriuretic peptides in coronary vasculature and ischaemic myocardium

The natriuretic peptides are a family of widely distributed polypeptide mediators that exert a range of actions in several body systems. In cardiovascular homeostasis, the endocrine roles of the cardiac-derived atrial and B-type natriuretic peptide (ANP and BNP) in regulating central fluid volume and blood pressure have been recognised for two decades. However, there is a growing realisation that natriuretic peptide actions go far beyond their endocrine effects and that local (autocrine/paracrine) regulatory actions within the heart and coronary vasculature may be of comparable importance, especially in disease states where tissue and circulating levels of the peptides rise markedly. In acute myocardial ischaemia, release of BNP occurs rapidly from ventricular myocardium, prompting speculation that the early activation of the natriuretic peptide receptor/cGMP signalling system may be an important autocrine/paracrine response in cardiac ischaemia. The autocrine/paracrine actions include inotropic effects, the acute regulation of coronary vascular tone and the attenuation of the susceptibility of myocardium to ischaemic injury. The effects of longer-term upregulation of natriuretic peptide expression in the heart could include the suppression of growth and proliferative responses in a variety of myocardial and vascular cells. In a variety of preparations, acute exposure of epicardial coronary arteries to pharmacological concentrations of natriuretic peptides evokes vasorelaxation, although in coronary microvessels, evidence for a vasorelaxant action of the peptides is less consistent. The mechanisms of the coronary vasorelaxant action are unclear but limited evidence suggests an endothelium-dependent component. In ischaemic myocardium, acute treatment with BNP prior to and during coronary artery occlusion exerts a markedly protective, concentration-dependent infarct-limiting action. This cytoprotective effect of the natriuretic peptide signalling pathway might conceivably represent an alternative endogenous salvage pathway in myocardium which is potentially exploitable therapeutically. Taken together, the acute actions of natriuretic peptides on the coronary vasculature and in myocardial ischaemia suggest a profile of activity that may be therapeutically beneficial in the management of patients with acute coronary syndromes.