BNP的临床应用价值

B型钠尿肽(Brain natriuretic peptide,BNP,又称脑钠素)是继心钠素(ANP)后利钠肽系统的又一成员,由于它首先是由日本学者Sudoh等于1988年从猪脑分离出来的因而得名,而实际上它主要来源于心室。BNP是一个由32个氨基酸残基构成的多肽类神经激素,分子量为3500。其氨基端第7位和第23位氨基酸残基(均为半胱氨酸)通过二硫键形     

血清NF-κB、BNP水平与室性心律失常患者莫雷西嗪治疗效果的关系

目的:观察血清核转录因子κB(Nuclear factor-kappa B,NF-κB)、B型钠尿肽(B type natriuretic peptide,BNP)水平在室性心律失常(Ventricular arrhythmias,VA)患者中的表达,并分析二者与莫雷西嗪治疗效果的关系.方法:选取2018年8月至202...     

ANP及其受体NPR-A与肿瘤关系的研究进展

近年来心房钠尿肽(atrial natriuretic peptide,ANP)及ANP受体(natriuretic peptide receptor A,NPR-A)在肿瘤研究中广受关注。ANP及其受体NPR-A的研究为肿瘤的治疗提供新思路,NPR-A有望成为肿瘤治疗的药物作用靶点。该文将对ANP及NPR-A在肿瘤发生、发展中的作用作一综述。     

大肠杆菌β-半乳糖苷酶ED片段与人B型钠尿肽抗原的共表达

B型钠尿肽(B-type natriuretic peptide,BNP)又称脑钠肽(brain natriuretic peptide),是心室分泌的激素样短肽,具有利尿利钠效应,能够舒张血管、抑制醛固酮分泌及肾素活性[1].血浆BNP水平已被证实是充血性心力衰竭诊断和预后判断的生物标志物.     

心力衰竭患者血浆B型钠尿肽测定的临床意义

目前对心力衰竭(heart failure,HF)的诊断及治疗的血液标志物主要有:钠尿肽类(ANP、BNP、CNP、VNP)、强心类固醇(DLIF、OLF)、细胞因子﹙TNF-α、IL-6﹚以及肾上腺髓质素、瘦素及肌钙蛋白等,这些血液标志物在HF的诊断和治疗中有各自的敏感性和特异性,现在钠尿肽已由科研转为HF诊断的常规项目.本文通过测定95例HF患者血浆BNP(B-type natriuretic peptide,BNP)的含量,以探讨其在诊断中的意义. 1 对象和方法 1.1 对象 1.1.1 HF组选择2005年12月～2007 年2月在我院就诊的门诊及住院患者95例(男59,女36),年龄(20～76)岁,平均57.6岁.按纽约心脏协会(NYHA)心功能分级标准诊断和分型.Ⅰ级30例,Ⅱ级 30例,Ⅲ级20 例,Ⅳ级15例.     

B型钠尿肽的研究进展

型钠尿肽(B-type natriutetic peptide，BNP)是1988年由日本学者从猪脑内分离出来的一种利钠多肽，又称脑钠肽(Brain natriutetic peptide)。与心房肽(ANP)相似，具有利尿、利钠、扩张血管和降压作用，是心钠素家族中的新成员。它是一种主要由心室合成、分泌的心脏激素。能敏感而特异地反映左心室功能变化，在心血管疾病的发病、诊断、治疗以及预后等方面均有重要的意义。本文就其生化、生理和临床应用进展综述如下。     

心房钠尿肽对缺血再灌注损伤心肌的保护作用及其机制探讨

<正>目的:研究心房钠尿肽(atrial natriuretic peptide,ANP)对缺血再灌注损伤心肌的保护作用及其作用机制。方法:SD大鼠随机分为正常组、对照组及ANP组;通过Langendorff灌流装置建立大鼠离体心脏缺血再灌注模型,计算出各组缺血心脏的梗死面积,并利用化学比色法测定各组心脏组织中乳酸(LD)、超氧化物歧化酶(SOD)活性以及丙二醛(MDA)含量。结果:ANP     

静脉注射IL-19重组质粒对大鼠实验性自身免疫性心肌炎的治疗作用

目的:评估静脉注射白细胞介素19(interleukin-19,IL-19)重组质粒对大鼠实验性自身免疫性心肌炎(experimental autoimmune myocarditis,EAM)的治疗作用。方法:将猪心室肌球蛋白与等体积完全弗氏免疫佐剂充分混匀后,双足皮下注射制作大鼠EAM模型,免疫后第6天应用静脉注射方法将IL-19重组质粒导入体内,第17天行心脏超声检查后处死大鼠,检测心脏重量与体重比值、病理学评估、心肌炎面积率;实时荧光定量PCR检测心衰标记物心房钠尿肽(atrial natriuretic peptide,ANP)、脑钠尿肽(brain natriuretic peptide,BNP)的表达水平,进一步检测心肌相关炎症因子IL-18、IL-1β、IL-12p35和IFN-γ的表达水平。结果:IL-19重组质粒导入组的大鼠心功能得到显著改善;心脏重量体重比、心肌炎面积率、ANP、BNP的表达均较模型组明显下降;相关炎症细胞因子的表达也显著降低。结论:应用静脉注射法进行IL-19重组质粒体内导入治疗,明显抑制大鼠实验性自身免疫性心肌炎的炎症反应,减轻了心肌损伤从而改善心功能。     

MPV与冠心病心力衰竭患者预后的相关性研究

目的 探讨血小板平均体积(mean platelet volume,MPV)与冠心病心衰患者预后的相关性,同时评价MPV是否可以提供独立于N末端B型钠尿肽原(N-terminal pro-brain natriuretic peptide,NT-proBNP)以外的预后信息.方法 选择阜外医院因冠心病心衰的住院患者503例,记录他们入院时的NT-proBNP、MPV、左室射血分数(left ventricular ejection fraction,LVEF)以及其他临床指标.随访患者住院期间和出院后的死亡及再住院情况.结果 中位随访693天后,230例发生再住院和死亡事件.多变量分析可以看出,MPV是冠心病心衰预后的独立危险因素[HR:1.220(1.048,1.419),P=0.017];在Kaplan-Meier分析中,将受试者以MPV、NT-proBNP中位数为分界线分2组,发现MPV、NT-proBNP低于中位数组的生存率显著高于MPV、NT-proBNP高于中位数组,COX风险回归模型显示,MPV＞10.3％且NT-proBNP＞1248.4fmol/mL组发生终点事件的风险比为4组中最高[HR:7.32(4.37,17.52)].结论 联合MPV和NT-proBNP检测可以提高单独检测NT-proBNP对心衰患者死亡的预测价值,提供独立于NT-proBNP以外的预测信息.     

CNP/NPR-B/cGMP信号通路调控雌性生殖过程

C型利钠肽(C-type natriuretic peptide,CNP)与其特异性受体利钠肽受体B(natriuretic peptide receptor B,NPR-B)结合并催化下游第二信使环磷酸鸟苷(cyclic guanosinc monophosphate,cGMP)生成,形成CNP/NPR-B/cGMP信号通路,从而介导多种生物学效应.近年来大量研究证实,CNP/NPR-B/cGMP信号通路与卵泡发育、卵母细胞减数分裂与成熟及胚胎着床和发育关系密切,提示此信号通路可能在雌性生殖过程中发挥显著作用.     

Natriuretic peptide C receptor signalling in the heart and vasculature

Natriuretic peptides (NPs), including atrial, brain and C-type natriuretic peptides (ANP, BNP and CNP), bind two classes of cell surface receptors: the guanylyl cyclase-linked A and B receptors (NPR-A and NPR-B) and the C receptor (NPR-C). The biological effects of NPs have been mainly attributed to changes in intracellular cGMP following their binding to NPR-A and NPR-B. NPR-C does not include a guanylyl cyclase domain. It has been denoted as a clearance receptor and is thought to bind and internalize NPs for ultimate degradation. However, a substantial body of biochemical work has demonstrated the ability of NPR-C to couple to inhibitory G proteins (Gi) and cause inhibition of adenylyl cyclase and activation of phospholipase-C. Recently, novel physiological effects of NPs, mediated specifically by NPR-C, have been discovered in the heart and vasculature. We have described the ability of CNP, acting via NPR-C, to selectively inhibit L-type calcium currents in atrial and ventricular myocytes, as well as in pacemaker cells (sinoatrial node myocytes). In contrast, our studies of the electrophysiological effects of CNP on cardiac fibroblasts demonstrated an NPR-C-Gi-phospholipase-C-dependent activation of a non-selective cation current mediated by transient receptor potential (TRP) channels. It is also known that CNP and BNP have important anti-proliferative effects in cardiac fibroblasts that appear to involve NPR-C. In the mammalian resistance vessels, including mesenteric and coronary arteries, CNP has been found to function as an NPR-C-dependent endothelium-derived hyperpolarizing factor that regulates local blood flow and systemic blood pressure by hyperpolarizing smooth muscle cells. In this review we highlight the role of NPR-C in mediating these NP effects in myocytes and fibroblasts from the heart as well as in vascular smooth muscle cells.     

Expression and glucocorticoid regulation of natriuretic peptide clearance receptor (NPR-C) mRNA in rat brain and choroid plexus

The natriuretic peptide clearance receptor (NPR-C) binds atrial natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide with high affinity. This receptor lacks an intracellular guanylate cyclase domain, and is believed to exert biological actions by sequestration of released natriuretic peptides and/or inhibition of adenylate cyclase. The present report summarizes the first detailed mapping of NPR-C mRNA in rat brain. In situ hybridization analysis revealed high levels of NPR-C mRNA expression in frontal and retrosplenial granular cortices, medial preoptic nucleus, ventral cochlear nucleus and choroid plexus. NPR-C mRNA expression was also observed in deep layers of neocortex and limbic cortex, posterior cortical amygdala, ventral subiculum, amygdalohippocampal area, and dentate gyrus. Positive hybridization signal was observed in both anterior and intermediate lobes of the pituitary gland. Regulatory studies indicated that expression of NPR-C mRNA was increased in the medial preoptic nucleus of adrenalectomized rats, suggesting negative glucocorticoid regulation. No changes in NPR-C mRNA expression were observed in frontal cortex or choroid plexus. These results suggest a role for the NPR-C in modulation of natriuretic peptide availability and/or adenylate cyclase activity in a subset of central natriuretic peptide circuits concerned with cortical, olfactory and neuroendocrine functions. Response of the NPR-C gene to changes in circulating hormones suggests the capacity for glucocorticoid modulation of natriuretic peptide action at the receptor level.     

Molecular mechanisms underlying cardiac antihypertrophic and antifibrotic effects of natriuretic peptides

Natriuretic peptides (NPs) exert well-characterized protective effects on the cardiovascular system, such as vasorelaxation, natri- and diuresis, increase of endothelial permeability, and inhibition of renin–angiotensin–aldosterone system. It has been reported that they also possess antihypertrophic and antifibrotic properties and contribute actively to cardiac remodeling. As a consequence, they are involved in several aspects of cardiovascular diseases. Antihypertrophic and antifibrotic actions of NPs appear to be mediated by specific signaling pathways within a more complex cellular network. Elucidation of the molecular mechanisms underlying the effects of NPs on cardiac remodeling represents an important research objective in order to gain more insights on the complex network leading to cardiac hypertrophy, ventricular dysfunction, and transition to heart failure, and in the attempt to develop novel therapeutic agents. The aim of the present article is to review well-characterized molecular mechanisms underlying the antihypertrophic and antifibrotic effects of NPs in the heart that appear to be mainly mediated by guanylyl cyclase type A receptor. In particular, we discuss the calcineurin/NFAT, the sodium exchanger NHE-1, and the TGFβ1/Smad signaling pathways. The role of guanylyl cyclase type B receptor, along with the emerging functional significance of natriuretic peptide receptor type C as mediators of CNP antihypertrophic and antifibrotic actions in the heart are also considered.     

Distribution of natriuretic peptide receptor-C immunoreactivity in the rat brainstem and its relationship to cholinergic and catecholaminergic neurons

The natriuretic peptide receptor type C (NPR-C) binds all natriuretic peptides. It is thought to be involved in the clearance of natriuretic peptides and more recently has been defined as essential for the neuromodulatory effects of natriuretic peptides. Although the distribution of NPR-C mRNA has been reported in the rat forebrain, there are no data on the distribution of NPR-C in the brainstem. We report an immunofluorescence study on the distribution of NPR-C immunoreactivity in the rat brainstem, and its presence in cholinergic and catecholaminergic neurons. NPR-C immunoreactivity was detected in several regions, including the periaqueductal gray, oculomotor nucleus, red nucleus and trochlear nucleus of the midbrain; the pontine nucleus, dorsal tegmental nucleus, vestibular nucleus, locus coeruleus, trigeminal motor nucleus, nucleus of the trapezoid body, abducens nucleus and facial nucleus of the pons; and the dorsal motor nucleus of the vagus, hypoglossal nucleus, lateral reticular nucleus, nucleus ambiguus and inferior olivary nucleus of the medulla oblongata. Interestingly, NPR-C immunoreactivity was detected in the cholinergic neurons of the oculomotor nucleus, trochlear nucleus, dorsal tegmental nucleus, motor trigeminal nucleus, facial nucleus, dorsal motor nucleus of the vagus, nucleus ambiguus and hypoglossal nucleus. Furthermore, NPR-C immunoreactivity was detected in several catecholaminergic neuronal groups including the A6, A5, A1, C3 and C1 cell groups. These results are consistent with an important role for natriuretic peptides in neuroendocrine regulation and central cardiovascular integration. The extensive distribution of NPR-C in the brainstem supports the hypothesis that NPR-C is involved in the neuromodulatory effect of natriuretic peptides.     

C-type natriuretic peptide inhibits L-type Ca2+ current in rat magnocellular neurosecretory cells by activating the NPR-C receptor

Magnocellular neurosecretory cells (MNCs), of the paraventricular and supraoptic nuclei of the hypothalamus, secrete the hormones vasopressin and oxytocin. As a result, they have an essential role in fundamental physiological responses including regulation of blood volume and fluid homeostasis. C-type natriuretic peptide (CNP) is present at high levels in the hypothalamus. Although CNP is known to decrease hormone secretion from MNCs, no studies have examined the role of the natriuretic peptide C receptor (NPR-C) in these neurons. In this study, whole cell recordings from acutely isolated MNCs, and MNCs in a coronal slice preparation, show that CNP (2 x 10(-8) M) and the selective NPR-C agonist, cANF (2 x 10(-8) M), significantly inhibit L-type Ca2+ current (I(Ca(L))) by approximately 50%. This effect on I(Ca(L)) is mimicked by dialyzing a G(i)-activator peptide (10(-7) M) into these cells, implicating a role for the inhibitory G protein, G(i). These NPR-C-mediated effects were specific to I(Ca(L)). T-type Ca2+ channels were unaffected by CNP. Current-clamp experiments revealed the ability of CNP, acting via the NPR-C receptor, to decrease (approximately 25%) the number of action potentials elicited during a 500 ms depolarizing stimulus. Analysis of action potential duration revealed that CNP and cANF significantly decreased 50% repolarization time (APD50) in MNCs. In summary, our findings show that CNP has a potent and selective inhibitory effect on I(Ca(L)) and on excitability in MNCs that is mediated by the NPR-C receptor. These data represent the first electrophysiological evidence of a functional role for the NPR-C receptor in the mammalian hypothalamus.     

NPR-C: a component of the natriuretic peptide family with implications in human diseases

The natriuretic peptide (NP) family includes atrial natriuretic peptide (ANP), B-type natriuretic peptide, C-type natriuretic peptide and their receptors NPR-A, NPR-B and NPR-C. The effects exerted by this hormonal system in the control of cardiovascular, renal and endocrine functions have been extensively investigated. Moreover, the involvement of NP in the pathogenesis of cardiovascular diseases has been demonstrated. Among the NP components, NPR-C has been described, at the time of its discovery, as the clearance receptor of NP devoid of any physiological functions. Emerging roles of NPR-C, however, have been highlighted over the last few years in relation to its effects on the cardiovascular system and other organs. These effects appear to be directly mediated through distinct cAMP-dependent intracellular mechanisms. Moreover, evidence has been accumulated on a potential pathophysiological role of NPR-C in human diseases. Ongoing studies from our group are revealing its involvement in the mediation of antiproliferative effects exerted on vascular cells by a molecular variant of human ANP. Thus, a new appraisal of NPR-C is overcoming the traditional view of a mere clearance receptor. This review focuses on the most important evidence supporting an involvement of NPR-C in mediating some of the actions of NP and its direct implication in cardiovascular diseases. The current state of knowledge highlights the need of further studies to better clarify the specific roles of NPR-C in pathophysiological processes.     

心肌缺血对大鼠延髓利钠肽受体表达的影响

 目的:探讨大鼠延髓腹侧部利钠肽受体A(NPR-A)、利钠肽受体C（NPR-C）、胆碱乙酰转移酶（ChAT）和酪氨酸羟化酶（TH）的表达在心肌缺血后不同时程的动态变化。方法:大鼠分为空白对照组、假手术组和模型组。建立心肌缺血模型后,于术后3、7、14、18和28 d取材,用Western blotting方法检测延髓腹侧部吻段、尾段内NPR-A、NPR-C、ChAT和TH表达。结果:在模型复制后的上述时点,延髓腹侧部NPR-A的表达显著升高（P<0.05）,NPR-C表达的升高晚于NPR-A,TH的表达显著低于空白对照组（P<0.05）,在延髓腹侧部吻段ChAT的表达低于空白对照组（P<0.05）,而在尾段与对照组无显著差异。结论:延髓心血管中枢内NPR-A和NPR-C的表达在心肌缺血后均显著升高,而ChAT和TH的表达则显著降低。利钠肽、ChAT和TH可能都参与了心肌缺血后心血管系统的植物神经调控。     

T-cell antigen receptor-mediated enhancement of the adenylate cyclase pathway depends on tyrosine protein kinases

We have examined the human T-cell line Jurkat the interaction between the activation through the T-cell receptor/CD3 complex and the adenylate cyclase pathway. OKT3, an anti-CD3 monoclonal antibody, did not activate by itself adenylate cyclase but produced a 3–7-fold increase of the cAMP accumulation induced by indirect (chloroadenosine, PGE₂) or direct (forskolin) agonists of adenylate cyclase. A more detailed study with forskolin showed that OKT3 enhanced the effect of low concentrations of the agonist without afffecting the maximal capacity of cAMP sysnthesis of the cells. The same concentrations of OKT3 produced both the enhancement of the adenylate cyclase pathway and the activation of phospholipase C. The enhancement of OKT3 of the adenylate cyclase pathway was inhibited by 0.5 μM staurosporine, a potent inhibitor of protein kinases, including tyrosine kinases and protein kinases C, whereas it was not inhibited by H7, a specific inhibitor of PKC. Staurosporine, at the same concentration, also inhibited the OKT3-induced activation of phospholipase C, a tyrosine kinase-dependent process. Taken together, these data that activation of T-cell through the T-cell receptor enhances the adenylate cyclase pathway by a tyrosine protein kinase-dependent mechanism.     

NPR-C protects embryonic stem cells from apoptosis by regulating p53 levels

The identification of intrinsic factors required for propagation of self-renewing embryonic stem (ES) cells is important to improve the efficiency of expansion of ES cells for therapeutic purposes. Here, we report a novel role for natriuretic peptide receptor-C (NPR-C) in the survival of murine ES cells. We found that NPR-C was highly expressed in ES cells and was downregulated during ES cell differentiation. Knockdown of NPR-C in ES cells by using a small-interfering RNA resulted in apoptotic cell death, and the induction of p53 protein expression. Conversely, chemical inhibition of p53 by α-pifithrin significantly reduced apoptosis in NPR-C-deficient cells. cANF((4-23)), a selective NPR-C agonist, protected ES cells against oxidative stress-induced apoptosis, and blocked activation of p53 and Nanog suppression in the presence of DNA-damaging agents. Thus, NPR-C is required to control DNA damage-induced p53 levels to maintain ES cell self-renewal.