脑钠肽临床应用进展

脑钠肽(brain natriuretic peptide,BNP)是近年倍受关注的心血管生物标记物,BNP是一种主要由心脏分泌的肽类激素,在心脏维持其正常结构和功能的中起着重要的作用,它具有利钠、利尿、扩血管、降压、拮抗RAAS系统、抑制交感神经兴奋等作用.它已超过原来仅作为心衰的诊断检测指标范畴.研究表明BNP与呼吸困难的鉴别诊断、心肌梗死、高血压、心房颤动、心肌病、肺栓塞等关系密切,现就BNP的临床研究进展作一综述.     

N 端脑钠肽前体在心血管疾病中的研究进展

N端脑钠肽前体(NT-proBNP)为脑钠肽(BNP)生成过程中产生的无活性肽段残片,其与BNP等摩尔量分泌。近年来,NT-proBNP的检测在心血管领域的作用越来越得到国内外学者的关注。NT-proBNP在心血管疾病的诊断、预后、分级等方面都具有重要的价值。本文主要介绍NT-proBNP在心血管疾病中的研究进展。     

N端脑钠肽前体在心血管疾病中的研究进展

N端脑钠肽前体（NT-proBNP）为脑钠肽（BNP）生成过程中产生的无活性肽段残片,其与BNP等摩尔量分泌。近年来,NT-proBNP的检测在心血管领域的作用越来越得到国内外学者的关注。NT-proBNP在心血管疾病的诊断、预后、分级等方面都具有重要的价值。本文主要介绍NT-proBNP在心血管疾病中的研究进展。     

脑钠肽及心肌活动指数在急性心肌梗死中的研究进展

脑钠肽(B type natrinretic peptides BNP)主要由心脏分泌的循环激素,具有扩血管利钠利尿抑制肾素醛固酮分泌的作用.急性心肌梗塞早期BNP即明显升高,对急性心肌梗塞患者预后有很好的指导作用;心肌活动指数(myocardial performance indexMPI)因不受超声条件、心脏几何形态、心室收缩及舒张压等影响,较之传统左室射血分数更为客观、准确,已被广泛应用于评价心功能.脑钠钛作为神经内分泌激素,心肌活动指数作为机械因素联合用于评价急性心肌梗死患者的预后及筛检急性冠脉事件的高危患者将起到更加重要的作用,本文现将两项指标在AMI最新研究进展作一综述.     

N末端脑钠肽前体在围冠状动脉搭桥术期的变化及意义

N-末端脑钠肽前体(N-terminal pro brain natriuretic peptide,NT-proBNP)是体内脑钠肽前体(proBNP)裂解成脑钠肽(brain natriuretic peptide,BNP)时的产物,NT-proBNP的血浆浓度及稳定性比BNP更高,半衰期更长,属于钠尿肽系统的重要一员,本身无生物学活性。NT-proBNP主要由正常的心肌细胞合成和分泌,在心肌损伤或坏死后迅速升高,可反映机体代偿病理改变和恢复循环的能力,是心功能障碍性疾病,如心力衰竭、左室肥厚等诊断、疗效监测和预后评估等最佳的心肌标志物,临床通过测定血浆NT-proBNP水平用于急慢性充血性心力衰竭(congestive heart failure,CHF)的诊治及预后,本文主要就NT-proBNP在围冠状动脉搭桥术(Coronary Artery Bypass Grafting,CABG)期的变化及临床意义的新进展进行综述。     

冠心病患者的血浆大内皮素与N末端脑钠肽水平及其与心功能的关系

目的:探讨冠心病(CHD)患者血浆大内皮素(Bigendothelin-1,Big ET-1)与N末端脑钠肽(NT-pro BNP)的水平及其与心功能的关系。方法:选择本院2014年1月-2014年5月收治的60例CHD患者为观察组,及同期接受体检的60例健康志愿者作为对照组,测定并比较两组的血浆大内皮素与N末端脑钠肽水平以及不同心功能分级CHD患者的血浆大内皮素与N末端脑钠肽水平的差异,分析血浆大内皮素与N末端脑钠肽水平与CHD患者心功能的关系。结果:观察组患者血浆Big ET-1和NT-pro BNP的水平均显著高于对照组,差异具有统计学意义(P0.05)。随着CHD患者的心功能分级的增加,其血浆Big ET-1和NT-pro BNP的水平逐渐升高,且各组之间比较差异均具有统计学意义(P0.05)。血浆Big ET-1、NT-pro BNP水平与CHD患者的心功能之间存在明显的正相关性(P0.05)。结论:CHD患者的血浆Big ET-1与NT-pro BNP水平均异常升高,且与患者的心功能呈正相关,监测其水平对判断CHD的病情及心功能可能具有重要的临床参考价值。     

脑利钠肽后处理对兔急性心肌梗死的保护作用

目的：脑利钠肽后处理对兔急性心肌梗死的保护作用及可能机制。方法：30 只兔随机分为3 组,每组10 只,左冠状动脉的左 室支缺血30 分钟,再灌注120 分钟。AMI（急性心肌梗死）组：再灌注期间静脉滴注生理盐水;BNP（脑利钠肽）组：再灌注期间静脉 滴注rhBNP(重组人脑利钠肽);BNP+GLY（脑利钠肽+格列苯脲）组：再灌注期间静脉滴注rhBNP,同时舌下静脉注射GLY 。连续 监测心电变化,统计再灌注120 min 室性心动过速(VT)、心室颤动(VF)的发生率。心肌再灌注120 min 后,分别测定SOD(超氧化 物歧化酶)、MDA（丙二醛）、cTnI（肌钙蛋白I）、CK-MB（肌酸激酶同工酶）。各组随机抽取2 只兔,分别于再灌注1 小时和2 小时末 取心尖组织,HE 染色。结果：（1）再灌注心律失常：BNP 组与AMI组比较,VT 和VF发生率均明显升高（均为P<0.01）;BNP+GLY 组与BNP 组比较,VT 和VF 发生率均明显升高（均为P<0.01）。（2）SOD、MDA、cTnI 和CK-MB 水平：BNP 组与AMI 组比较, MDA、cTnI 和CK-MB 均明显降低（均为P<0.01）,而SOD 明显升高（P<0.01）;BNP+GLY 组与BNP 组比较,MDA、cTnI 和 CK-MB 均明显升高（分别为P<0.01,P<0.05和P<0.01）,而SOD明显降低（P<0.01）。（3）心肌HE 染色：AMI组和BNP+GLY 组心 肌损伤明显,BNP 组心肌损伤轻微。结论：脑利钠肽后处理对兔急性心肌梗死（缺血- 再灌注损伤）具有保护作用,可能与KATP 通道相关。     

急性心肌梗死患者肠道优势菌群分析

目的探讨急性心肌梗死患者肠道优势菌群的改变及其与疾病严重程度的关系。方法共筛选急性心肌梗死患者71名及正常健康体检者33名,急性心肌梗死患者根据是否心衰分为急性心肌梗死组36名和急性心肌梗死伴泵衰竭组35名,所有入选者收集大便及血清标本,分别采用qPCR及化学发光仪测定肠道优势菌群改变和血清脑钠肽前体及肌钙蛋白水平。结果急性心肌梗死患者肠道优势菌群显著改变,肠道肠杆菌以及肠球菌细菌数量较对照组显著增加,均与脑钠肽前体、肌钙蛋白、Killip分级显著正相关,而双歧杆菌、乳酸杆菌等细菌数量显著降低,与脑钠肽前体、肌钙蛋白、Killip分级显著负相关。结论急性心肌梗死患者呈现典型的肠道菌群紊乱,且与患者疾病严重程度相关。     

急性缺血性脑卒中患者入院时血浆BNP水平与梗死部位关系

目的:分析急性缺血性脑卒中患者入院时血浆脑钠肽(BNP)水平与缺血性脑卒中梗死部位的关系。方法:随机入选88例急性缺血性脑卒中患者,按梗死部位,将其分为前循环病灶组(66名)和后循环病灶组(22名)两组进行比较。测定入院时血浆脑钠肽(BNP)水平进行比较。两组脑卒中病人的危险因素血糖、糖化血红蛋白、血脂全套,肝肾功能分析对比,并将急性缺血性脑卒中患者梗死部位相关的多个变量采用单因素logistic回归分析。结果:前循环病灶组血浆脑利钠肽水平的中位数是225.90 pg/mL,四分位数间距为596.00 pg/mL;后循环病灶组的中位数是750.95 pg/mL,四分位数间距为907.00 pg/mL。后循环病灶组血浆脑利钠肽水平要显著高于前循环病灶组血浆脑利钠肽水平,两个部位间入院时的脑利钠肽水平有统计学差异(P=0.004)。通过入院时脑利钠肽水平与缺血性脑卒中梗死部位的关系的ROC曲线,得出截点299.50 pg/mL。入院时血浆脑利钠肽水平≥299.50 pg/mL可以作为后循环病灶组的预测指标,其敏感性72.72%,特异性62.12%。结论:急性缺血性脑卒中患者入院时血浆BNP水平可作为急性期区别前后循环脑梗死的预测因子。     

急性缺血性脑卒中患者入院时血浆BNP水平与梗死部位关系

目的：分析急性缺血性脑卒中患者入院时血浆脑钠肽（BNP）水平与缺血性脑卒中梗死部位的关系。方法：随机入选88例急性缺血性脑卒中患者,按梗死部位,将其分为前循环病灶组（66名）和后循环病灶组（22名）两组进行比较。测定入院时血浆脑钠肽（BNP）水平进行比较。两组脑卒中病人的危险因素血糖、糖化血红蛋白、血脂全套,肝肾功能分析对比,并将急性缺血性脑卒中患者梗死部位相关的多个变量采用单因素logistic回归分析。结果：前循环病灶组血浆脑利钠肽水平的中位数是225.90 pg/mL,四分位数间距为596.00 pg/mL;后循环病灶组的中位数是750.95 pg/mL,四分位数间距为907.00 pg/mL。后循环病灶组血浆脑利钠肽水平要显著高于前循环病灶组血浆脑利钠肽水平,两个部位间入院时的脑利钠肽水平有统计学差异（P=0.004）。通过入院时脑利钠肽水平与缺血性脑卒中梗死部位的关系的ROC曲线,得出截点299.50 pg/mL。入院时血浆脑利钠肽水平≥299.50 pg/mL可以作为后循环病灶组的预测指标,其敏感性72.72%,特异性62.12%。结论：急性缺血性脑卒中患者入院时血浆BNP水平可作为急性期区别前后循环脑梗死的预测因子。     

Pathophysiological significance and clinical application of ANP and BNP in patients with heart failure

Plasma levels of ANP and BNP increase in accordance with the severity of the heart failure. In severe cases, the amount of BNP secreted surpasses that of ANP. The main secretion site of BNP is the ventricles, and that of ANP is the atria. However, ANP is also secreted from the ventricles as heart failure advances, and thus the ventricles are important sites for both BNP and ANP. It is well known that myocardial stretch is a key factor in the stimulation of the secretion of ANP and BNP, although neurohumoral factors also play a role in the secretion mechanism. The major physiological effects of ANP and BNP are vasodilation, natriuresis, and inhibition of the renin-angiotensin-aldosterone (RAA) and the sympathetic nervous systems; all of which are supposed to suppress the progression of heart failure. The inhibitory action of ANP and BNP on the RAA system has been considered to be an extra-cardiac effect. We recently reported the activation of an angiotensin-converting enzyme and aldosterone production in failing human hearts. ANP and BNP, however, would inhibit aldosterone production, not only in the adrenal cortex but also in cardiac tissue. ANP, and especially BNP, are useful markers of the heart's status during treatment for heart failure. The infusion of synthetic ANP (hANP) or BNP (Nesiritide) is effective in the treatment of acute heart failure. In Japan, BNP occupies an important position in the diagnosis of chronic heart failure, as ANP does in the treatment of acute heart failure.     

Tachycardia-induced myocardial ischemia and diastolic dysfunction potentiate secretion of ANP, not BNP, in hypertrophic cardiomyopathy

The aim of this study was to investigate what factor determines tachycardia-induced secretion of atrial and brain natriuretic peptides (ANP and BNP, respectively) in patients with hypertrophic cardiomyopathy (HCM). HCM patients with normal left ventricular (LV) systolic function and intact coronary artery (n = 22) underwent rapid atrial pacing test. The cardiac secretion of ANP and BNP and the lactate extraction ratio (LER) were evaluated by using blood samples from the coronary sinus and aorta. LV end-diastolic pressure (LVEDP) and the time constant of LV relaxation of tau were measured by a catheter-tip transducer. These parameters were compared with normal controls (n = 8). HCM patients were divided into obstructive (HOCM) and nonobstructive (HNCM) groups. The cardiac secretion of ANP was significantly increased by rapid pacing in HOCM from 384 +/- 101 to 1,268 +/- 334 pg/ml (P < 0.05); however, it was not significant in control and HNCM groups. In contrast, the cardiac secretion of BNP was fairly constant and rather significantly decreased in HCM (P < 0.01). The cardiac ANP secretion was significantly correlated with changes in LER (r = -0.57, P < 0.01) and tau (r = 0.73, P < 0.001) in HCM patients. Tachycardia potentiates the cardiac secretion of ANP, not BNP, in patients with HCM, particularly when it induces myocardial ischemia and LV diastolic dysfunction.     

Augmented secretion of brain natriuretic peptide in acute myocardial infarction.

In order to elucidate biosynthesis and secretion of natriuretic peptides in the early phase of acute myocardial infarction (AMI), we measured the plasma level of brain natriuretic peptide (BNP), a novel cardiac hormone secreted from the ventricle, in patients with AMI and compared with that of atrial natriuretic peptide (ANP). The plasma level of BNP increased rapidly (within hours from the onset of AMI) and markedly (greater than 100 times the normal level) as compared to that of ANP. The plasma ANP level correlated with pulmonary capillary wedge pressure (PCWP), whereas the plasma BNP level did not correlate with PCWP but highly correlated inversely with cardiac index. These results indicate that BNP is secreted from the heart much more acutely and prominently than ANP in the early phase of AMI, in association with left ventricular dysfunction.     

急性心肌梗死患者早期血浆脑钠肽水平与左室重构及预后关系的评估

目的：探讨急性心肌梗死（AMI）早期脑钠肽（BNP）水平与左室重构及预后的关系。方法：用放射免疫法测定AMI患者早期血浆BNP水平;用超声心动图检查测量左室收缩末容积（ESV）、左室舒张末容积（EDV）、射血分数（EF）并通过计算得左室质量（LVM）。并根据左心室容积指标分组,左心室容积增加率〉20%为左心室重构组,否则为非重构组,比较两组血浆BNP水平。结果：重构组恢复期左心室舒张末期及收缩末期容积指数均高于非重构组（P〈0.01）,亦高于急性期左心室容积（P〈0.01）。重构组早期血浆BNP浓度明显高于非重构组（P〈0.01）,恢复期也较非重构组高（P〈0.01）。重构组早期BNP浓度与恢复期左心室容积及容积变化量之间呈正相关。结论：AMI早期BNP升高与急性期左室重构密切相关,血浆BNP浓度可以作为溶栓治疗再通的观察指标及预后判断依据。     

Relation of B-type natriuretic peptide to left ventricular wall stress as assessed by cardiac magnetic resonance imaging in patients with dilated cardiomyopathy

Ventricular loading conditions are crucial determinants of cardiac function and prognosis in heart failure. B-type natriuretic peptide (BNP) is mainly stored in the ventricular myocardium and is released in response to an increased ventricular filling pressure. We examined, therefore, the hypothesis that BNP serum concentrations are related to ventricular wall stress. Cardiac magnetic resonance imaging (MRI) was used to assess left ventricular (LV) mass and cardiac function of 29 patients with dilated cardiomyopathy and 5 controls. Left ventricular wall stress was calculated by using a thick-walled sphere model, and BNP was assessed by immunoassay. LV mass (r = 0.73, p < 0.001) and both LV end-diastolic (r = 0.54, p = 0.001) and end-systolic wall stress (r = 0.66, p < 0.001) were positively correlated with end-diastolic volume. LV end-systolic wall stress was negatively related to LV ejection fraction (EF), whereas end-diastolic wall stress was not related to LVEF. BNP concentration correlated positively with LV end-diastolic wall stress (r = 0.50, p = 0.002). Analysis of variance revealed LV end-diastolic wall stress as the only independent hemodynamic parameter influencing BNP (p < 0.001). The present approach using a thick-walled sphere model permits determination of mechanical wall stress in a clinical routine setting using standard cardiac MRI protocols. A correlation of BNP concentration with calculated LV stress was observed in vivo. Measurement of BNP seems to be sufficient to assess cardiac loading conditions. Other relations of BNP with various hemodynamic parameters (e.g., EF) appear to be secondary. Since an increased wall stress is associated with cardiac dilatation, early diagnosis and treatment could potentially prevent worsening of the outcome.     

急性心力衰竭患者就诊时血压心率及血浆BNP水平与心功能的关系分析

目的:探讨急性心力衰竭(AHF)患者就诊时血压心率及血浆脑钠肽(BNP)水平与心功能的关系。方法:选取2013年4月-2014年12月于本院治疗的AHF患者134例,于就诊时测量患者血压、心率、BNP及心脏超声相关指标,分析血压心率及血浆BNP水平与心功能的关系。结果:就诊时SBP水平与左心室舒张末期直径及每搏输出量呈现正相关性(r=0.134、0.238,均P0.05);心率与每搏输出量、左室缩短率以及射血分数呈现负相关性(r=-0.177,-0.231,-0.197,均P0.05);BNP水平与左心室舒张末直径成正相关性,与左室缩短率以及射血分数呈负相关性(r=0.150、-0.247、-0.271,均P0.05)。结论:血压、心率以及BNP是临床诊断、评估AHF的重要指标。     

Human bone marrow endothelial cells: a new identified source of B-type natriuretic peptide

B-type natriuretic peptide (BNP) is a hormone mainly secreted by cardiac ventricle myocytes and which is increased in cardiac diseases. Moreover, BNP expression has been shown in various cell/tissue types. Six different human endothelial cell (EC) culture models arising from macro and microcirculation either primary cultures or cell lines were cultured and screened for BNP presence and secretion. All cell types expressed BNP mRNA while only the ECs arising from bone marrow stromal compartment secreted high amounts of BNP protein. This report is the first to identify ECs as a new source of BNP. However, BNP secretion is limited to a particular EC type.     

Increased secretion of brain natriuretic peptide and atrial natriuretic peptide, but not sufficient to induce natriuresis in rats with nephrotic syndrome.

The levels of immunoreactive brain natriuretic peptide (ir-BNP) and immunoreactive atrial natriuretic peptide (ir-ANP) were evaluated by radioimmunoassay in both the atrium, ventricle and plasma of adriamycin-induced nephrotic rats and control rats. There was no difference in right and left atrial concentrations of ir-BNP, however, a higher right atrial concentration of ir-ANP was observed in nephrotic rats than in controls (p less than 0.01). The ventricular ir-BNP and ir-ANP were increased in nephrotic rats compared to controls (BNP: p less than 0.001, ANP: p less than 0.001). Cardiac BNPs were composed of pro-BNP (gamma-BNP) and its C-terminal 45-amino-acid peptide (BNP-45). The ratio of BNP-45/gamma-BNP in nephrotic rats was higher than that of controls in both atria and in the ventricle. Plasma ir-BNP and ir-ANP were significantly higher in nephrotic rats than in controls (BNP: p less than 0.001, ANP: p less than 0.001), and each level was negatively correlated with urinary sodium excretion in nephrotic rats (BNP: r = -0.84, p less than 0.001, ANP: r = -0.88, p less than 0.001). These results suggest that production and secretion of both BNP and ANP are concomitantly stimulated by a decreased renal ability to eliminate sodium and water, but this secretion is insufficient to induce effective natriuresis in nephrotic rats.