急性心肌梗死患者血浆BNP、ET、CRP、ANP水平变化与临床观察分析

目的　观察急性心肌梗死 (AMI)患者血浆中B型钠尿肽 (BNP)、内皮素 (ET)、C 反应蛋白 (CRP)、A型钠尿肽 (ANP)水平变化 ,为治疗及预后判断提供依据。方法　应用酶联免疫法及免疫放射分析法对 4 6例AMI患者治疗前后和 30名正常对照者血浆中BNP、ET、CRP、ANP水平进行检测。结果　AMI患者血浆中BNP、ET、CRP、ANP治疗前后比较差异有显著性 (P <0 .0 0 1) ,正常对照组与AMI治疗前比较差异有显著性 (P<0 .0 0 1) ,BNP与CRP在AMI治疗前水平呈正相关 (r =0 .874 ) ,治疗后呈明显的下降趋势 (r =0 .6 5 4 ) ,AMI治疗前后ANP与ET呈正相关 ,但AMI经溶栓和相应的支持治疗后ANP基本恢复到正常水平 (P >0 .0 5 ) ,而BNP、ET、CRP水平虽然下降明显 ,但与正常组比较差异仍有显著性 (P <0 .0 5 )。结论　AMI患者血浆中BNP、ANP、ET、CRP水平的变化说明其参与了AMI的发生、发展 ,特别是冠状动脉粥样斑块的形成和 (或 )破裂及血栓形成 ,其炎症因子是主要因素。因此 ,4项指标的观察分析对AMI治疗、预后判断具有重要意义     

87例急性心肌梗死患者血浆B型钠尿肽水平检测分析

目的评价血浆B型钠尿肽(BNP)水平在急性心肌梗死(AMI)患者诊治中的临床价值。方法采用微粒子酶免疫分析方法分别测定健康者、其他疾病者以及AMI患者治疗前后血浆BNP水平,建立BNP在该方法下正常参考值并比较不同性别和不同年龄段的差异;分别比较AMI组与健康对照组和其他疾病组之间的差异以及AMI组患者治疗前后的差异。结果血浆BNP的正常参考值为10.31~58.66 pg/mL(x±1.96s),且在不同性别和不同年龄段差异不显著,AMI患者血浆BNP表达水平明显高于健康者和其他疾病者,分别比较差异具有统计学意义(P<0.001),再灌注治疗前后相互比较差异亦具有统计学意义(P<0.001)。结论血浆BNP水平的测定不仅能提高AMI的诊断准确率,而且在AMI的疗效观察、预后判断及评价血运是否重建等方面具有重要意义。     

血浆B型钠尿肽水平对冠心病左心室收缩功能不全的诊断价值

目的研究冠心病患者血浆B型钠尿肽(BNP)水平与左心室收缩功能的关系.方法用免疫发光法检测30名正常对照者与69例冠心病患者血浆BNP水平,通过纽约心脏病协会心功能分级标准(NYHA)及超声心动图结果对冠心病患者心功能分级.结果对照组、心功能Ⅰ～Ⅱ级组及心功能Ⅲ～Ⅳ级组的BNP水平分别为(31.56±21.48) μg/L、(105.52±91.77) μg/L和(433.18±378.03)μg/L,3组差异均有非常显著性(P<0.001).冠心病患者BNP水平与左室射血分数(LVEF)呈负相关(r=-0.70,P<0.001),其中LVEF≤40%亚组BNP水平显著高于LVEF>40%亚组(P<0.01).结论血浆BNP水平能反映冠心病患者左心室收缩功能,该指标对早期心功能不全患者的检出、心力衰竭程度的评判等具有重要的临床价值.     

急性心肌梗塞患者血浆心钠素、铜、锌含量变化的临床观察

本文测定了30例急性心肌梗塞(AMI)患者的血浆心钠素(ANP)和血清铜、锌的含量,结果显示,AMI患者血浆ANP明显高于对照组(p<0.01),连续观察四周均持续在较高的水平,而血清锌下降,铜则升高,铜/锌比值增大,与对照组问亦有非常显著的差异(P<0.001),对伴严重并发症者更为显著,提示测定AMI患者血浆ANP及血锌、铜含最有助于了解病变的严重程度与估计预后的参考指标。本文还提示ANP与锌呈负相关(r=-0.448,p<0.01),与铜呈正相关(r=0.851,p<0.001),这一相关性改变可能与体内内分泌、激素水平变化影响锌、铜的代谢有关。     

慢性肾功能衰竭患者血液透析前后血管活性因子的变化及临床意义

目的了解血液透析患者血浆一氧化氮（NO）、内皮素（ET）、心房利钠多肽（ANP）、肾素（PRA）及血管紧张素Ⅱ（ATⅡ）在透析前后的水平变化及临床意义。方法设正常对照、慢性肾功能不全失代偿期患者及慢性肾功能衰竭（CRF）患者各30例。用比色法测定NO,放射免疫法测定ANP、ET、PRA及ATⅡ水平。结果CRF组NO、ANP、ET、PRA、ATⅡ浓度明显高于对照组（P<0.05或P<0.01）;透析后NO和ANP显著下降（P<0.05和P<0.01）,PRA和ATⅡ浓度明显升高（P均<0.01）,ET透析前后无明显变化（P>0.05）。结论血液透析可使CRF患者血浆NO、ANP降低,PRA、ATⅡ升高,提示ET升高可增加ANP和PRA水平,ANP浓度可抑制ATⅡ的分泌。     

血浆纤维蛋白原与脑钠素在急性心肌梗死危险度评价中的研究

目的探究血浆纤维蛋白原(Fbg)和脑钠素(BNP)水平对急性心肌梗死(AMI)危险度的评价及与其之间的相互作用。方法以2016年10月至2017年10月该院心内科住院患者104例为研究对象,其中诊断为AMI患者为AMI组(n=64),其余为非AMI组(n=40),AMI组患者随访6个月,再根据是否发生不良事件分为事件组和对照组。采用化学发光法测定血浆中BNP水平;采用凝固法检测Fbg水平。分析血浆Fbg和BNP对AMI危险度的评价及与其之间的相互作用。结果 AMI组血浆Fbg、BNP水平高于非AMI组,差异有统计学意义(P0.05)。随冠状动脉危险程度逐渐加重,血浆Fbg与BNP水平均呈上升趋势,且冠状动脉病变严重程度与Fbg、BNP水平呈正相关(r=0.728,P0.001;r=0.824,P0.001)。6个月后随访AMI患者,事件组血浆Fbg、BNP水平高于对照组(P0.05),事件组心力衰竭血浆Fbg、BNP水平高于对照组,差异有统计学意义(P0.05)。Fbg诊断灵敏度为87.50%,特异度为62.50%,曲线下面积(AUC)为0.783;BNP诊断灵敏度为85.00%,特异度为54.68%,AUC为0.700;Fbg、BNP联合检测其诊断灵敏度为76.56%,特异度为80.00%,AUC为0.845。结论血浆Fbg、BNP水平能较好地反映患者心肌受损情况,预测病危程度与预后效果,有效指导AMI患者治疗方法的选择和改善患者预后评价。     

慢性肾衰竭血清晚期糖基化终产物水平的变化及意义

目的探讨慢性肾功能衰竭患者血清晚期糖基化终产物(AGEs)水平的变化、意义及高通量血透对AGEs的清除效果. 方法应用竞争性ELISA法检测慢性肾功能衰竭(CRF)患者(非血液透析组及血液透析组)血清AGEs 水平,同时测血浆脂质过氧化物丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性. 结果 CRF患者无论血液透析与否,血清AGEs均明显高于健康组(P均<0.001),非血液透析与血液透析组AGEs水平无显著性差异(P<0.05),AGEs水平与CRE呈明显正相关(r=0.5974,P<0.01),与血糖无相关性;CRF患者血浆MDA含量明显高于健康组(P均<0.001),SOD活性明显低于健康组(P<0.05).AGEs与MDA、SOD间无相关性;常规血液透析(CHD)组,透析前后血清AGEs水平无显著性差异 (P < 0.05),而高通量血液透析(HFHD)组透析后血清AGEs水平明显降低(P<0.001),两组血浆SOD活性均明显升高(P<0.01),MDA含量明显降低(P<0.01).结论 CRF时,因肾功能受损致AGEs清除障碍,是血清AGEs水平升高的主要原因,同时CRF时氧化应激增强可能也促进了AGEs生成.高通量血液透析可以有效清除血清AGEs,并改善自由基代谢紊乱.     

快速B型钠尿肽测定及在心衰诊断中的应用价值

目的探讨全自动免疫分析系统(Triage(R))快速定量检测B型钠尿肽(BNP)在心衰诊断中的应用价值.方法使用Triage(R) BNP测定法检测46例心力衰竭(CHF)患者和46名对照者全血BNP.结果 CHF患者BNP含量为(586.7±980.8)ng/L,对照组BNP含量为(36.6±37.7)ng/L,两者差异有显著性(Z=8.11,P<0.001).BNP水平随心功能NYHA分类级别增高而升高,各级间差异有显著性(χ2=29.75,P<0.001).BNP对CHF的诊断效率较高,ROC曲线下面积为0.948.结论 Triage(R)快速BNP检测可作为常规生化项目,为临床诊断CHF提供依据.     

血浆B型钠尿肽与血清C反应蛋白联合检测在慢性心力衰竭中的临床应用

目的探讨慢性心力衰竭(CHF)患者血浆B型钠尿肽(BNP)以及血清C反应蛋白(CRP)联合检测的临床应用价值。方法分别采用化学发光微粒子酶免疫分析法以及免疫浊度法测定89例CHF患者及40名健康对照者血浆BNP以及血清CRP浓度。依据美国纽约心脏病协会(New York Heart Association,NYHA)分级方案对CHF患者进行心功能分级。结果 CHF患者的血浆BNP及血清CRP浓度均明显高于健康对照组,差异有统计学意义(P<0.05)。CHF患者NYHA心功能Ⅰ～Ⅳ级血浆BNP及血清CRP浓度逐渐升高,NYHA各级之间各自的BNP浓度、CRP浓度比较,差异均有统计学意义(P<0.05);血浆BNP及血清CRP水平与NYHA分级间均存在明显的正相关(与BNP,r=0.835,P<0.01;与CRP,r=0.776,P<0.01)。结论 CHF患者血浆BNP及血清CRP水平随着心力衰竭严重程度的增加而升高,二者联合检测可以准确评价心功能,可作为临床诊断、疗效观察以及预后判断CHF的客观指标。     

急性脑梗死患者血浆BNP、IL-6及CRP水平变化及意义

目的:检测急性脑梗死患者血浆B型钠尿肽(BNP)、白介素-6(IL-6)及C-反应蛋白(CRP)水平变化,探讨其变化特点及与病情发生发展的关系。方法:用ELISA法和免役比浊法对56例急性脑梗死患者和63名健康正常人血BNP、IL-6及CRP水平进行检测。结果:脑梗死患者血清BNP、IL-6及CRP水平显著高于对照组(P<0.01),且其血浆BNP水平和CRP水平呈正相关(r=0.418,P<0.01)。结论:急性脑血管病(ACI)患者血浆BNP、IL-6及CRP水平明显升高。提示三者在ACI的发生发展中起重要作用。     

Head-to-head comparison of N-terminal pro-brain natriuretic peptide, brain natriuretic peptide and N-terminal pro-atrial natriuretic peptide in diagnosing left ventricular dysfunction

Brain natriuretic peptide (BNP), NT-proBNP and NT-pro-atrial natriuretic peptide (NT-proANP) were measured in blood samples from 57 patients using immunoassays and immunoradiometric assays to evaluate the usefulness as diagnostic markers for the detection of heart failure. For the detection of impaired left ventricular ejection fraction (LVEF), receiver operating characteristic curves showed that BNP had the best diagnostic performance with an area under curve (AUC) of 0.75±0.06. However, NT-proBNP (AUC: 0.67±0.07) and NT-proANP (AUC: 0.69±0.08) showed no significant difference to BNP. In a further analysis for the detection of resting LVEF <40%, BNP again was the best marker with an AUC of 0.83±0.06. NT-proBNP showed only a slightly smaller AUC (0.79±0.07). The AUC for NT-proANP was significantly smaller (0.65±0.08) compared to BNP. Additionally, BNP and NT-proBNP correlated negatively with the resting LVEF (BNP: −0.472, p<0.001; NT-proBNP: −0.306, p=0.026), whereas NT-proANP showed no significant correlation. In summary, BNP was the best marker to detect patients with impaired LVEF compared to NT-proBNP and NT-proANP. However, NT-proBNP showed no significant differences to BNP and it is therefore a new promising alternative marker for the detection of left ventricular dysfunction.     

Brain natriuretic peptide as a novel cardiac hormone in humans. Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide.

Using a specific radioimmunoassay for human brain natriuretic peptide (hBNP) with a monoclonal antibody, we have investigated its synthesis, secretion, and clearance in comparison with those of atrial natriuretic peptide (ANP) in normal subjects and patients with congestive heart failure (CHF). Mean BNP-like immunoreactivity (-LI) levels in normal atrium and ventricle were 250 and 18 pmol/g, respectively. The plasma BNP-LI level in normal subjects was 0.90 +/- 0.07 fmol/ml, which was 16% of the ANP-LI level. In contrast, the plasma BNP-LI level markedly increased in patients with CHF in proportion to its severity, and surpassed the ANP-LI level in severe cases. There was a significant step-up of the plasma BNP-LI level in the coronary sinus (CS) compared with that in the aortic root (Ao) and the difference between these BNP-LI levels, delta(CS-Ao)BNP, also increased with the severity of CHF. In addition, the step-up of the BNP-LI level in the anterior interventricular vein [delta(AIV-Ao)BNP] was comparable to delta(CS-Ao)BNP, indicating that BNP is secreted mainly from the ventricle. Predominant BNP synthesis in the ventricle was also confirmed by Northern blot analysis. Catheterization and pharmacokinetic studies revealed that hBNP is cleared from the circulation more slowly than alpha-hANP; this was in part attributed to lower (about 7%) binding affinity of hBNP to clearance receptors than that of alpha-hANP. A predominant molecular form of BNP-LI in the heart and plasma was a 3-kD form corresponding to hBNP. These results indicate that BNP is a novel cardiac hormone secreted predominantly from the ventricle, and that the synthesis, secretion and clearance of BNP differ from those of ANP, suggesting discrete physiological and pathophysiological roles of BNP in a dual natriuretic peptide system.     

N-terminal pro-C-type natriuretic peptide, but not C-type natriuretic peptide, is greatly elevated in the fetal circulation

We have identified recently a new peptide, NT-proCNP(1-50) (N-terminal pro-C-type natriuretic peptide), in the circulation of humans and sheep. A previous report of an elevated fetal-maternal gradient in immunoreactive CNP raised the possibility that processing and metabolism of proCNP may differ in maternal and fetal tissues. We therefore collected matching peripheral maternal and umbilical cord plasma samples at delivery from women with normotensive and pre-eclamptic pregnancies to investigate the presence and concentrations of CNP and NT-proCNP using HPLC and RIA. Plasma concentrations of NT-proCNP in normotensive umbilical cord plasma were 10-fold higher than maternal venous levels (246+/-17 compared with 24.3+/-1.8 pmol/l; P <0.001) and much higher than corresponding levels of CNP (3.6+/-0.4 compared with 1.8+/-0.3 pmol/l in the fetal and maternal plasma respectively; P <0.001). Although there was no significant difference between normotensive and pre-eclamptic plasma CNP concentrations in either maternal or umbilical cord blood, NT-proCNP showed a significant statistical interaction ( F =5.8, P =0.025) between the source (maternal or fetal) and gestational group (normotensive or pre-eclamptic). Maternal NT-proCNP levels were raised in the pre-eclampsia group, whereas the converse was observed in umbilical cord blood. In conclusion, the greatly elevated ratio of NT-proCNP/CNP in fetal compared with maternal plasma suggests that synthesis, as well as clearance, of CNP (but not NT-proCNP clearance) are markedly increased in fetal tissues.     

Pediatric brain natriuretic peptide and N-terminal pro-brain natriuretic peptide reference intervals

BACKGROUND: Brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) have been shown to be useful biomarkers for the diagnosis of heart failure. Pediatric reference intervals for these analytes have been reported in part. Previous studies lack large numbers in each group, have not covered all age ranges and have not compared results for BNP with NT-proBNP in simultaneously drawn samples. METHODS: We measured BNP in whole blood using the Biosite Triage point-of-care method and plasma NT-proBNP using the Dade RxL Dimension. We assessed between and within-day precision of both methods and after removing outliers employed the Hoffmann approach to calculate pediatric reference intervals over the age range of 0-21 y. We also compared the 2 methods on simultaneously drawn samples. RESULTS: Reference intervals revealed approximately 20-fold higher 97.5th percentiles for neonates than for children >3 y of age. 97.5th percentiles decreased significantly over the first 3 years of life. As shown by others, the CVs for the automated Dade RxL platform were somewhat lower than those for the POCT method. BNP and NT-proBNP correlated well in simultaneously drawn samples (r=0.947). DISCUSSION: Reference intervals for BNP and NT-proBNP are far higher in neonates and infants than in children older than three years of age. The reasons for this are unknown but resemble the elevated CK-MBs and troponins also found in neonates, although the 97.5th percentiles for these latter 2 cardiac markers decrease more rapidly to values found in older children by 6 months of age.     

Clearance of human brain natriuretic peptide in rabbits; effect of the kidney, the natriuretic peptide clearance receptor, and peptidase activity

Although the synthetic version of the cardiac peptide human brain natriuretic peptide (hBNP) has demonstrated beneficial cardiovascular effects in clinical studies, little is known about mechanisms governing its elimination from the blood. This study measured the role of the kidney, the natriuretic peptide clearance (NP-C) receptor, and peptidase digestion on the elimination of synthetic hBNP from the plasma compartment of rabbits. The estimated plasma steady state resulting from a continuous i.v. infusion was achieved within 50 min and was related in a linear manner with the infusion rate of the drug. Complete restriction of kidney blood flow by bilateral suture-ligation of the renal arteries compared with sham-treated animals reduced the clearance of hBNP by approximately half (24 +/- 9 ml/min versus 47 +/- 14 ml/min, respectively, p <. 007). Pharmacological blockade of the NP-C receptor with a clearance receptor-specific analog of atrial natriuretic peptide increased in a statistically significant and dose-related manner the plasma steady-state level of hBNP during continuous i.v. infusion of hBNP (maximum effect of 1.9 +/- 0.3-fold, p <.01). The peptidase inhibitor phosphoramidon increased in a dose-related manner the plasma steady-state level of hBNP 1.7 +/- 0.4-fold during continuous i.v. infusion of hBNP in rabbits. These data suggest that the kidney, the NP-C receptor, and peptidases are all important in the elimination of hBNP from the plasma compartment.     

Amino-terminal pro-brain natriuretic peptide, brain natriuretic peptide, and troponin T for prediction of mortality in acute heart failure

BACKGROUND: Combining testing for natriuretic peptides [amino-terminal pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP)] and cardiac troponin T (cTnT) may help predict mortality in patients with acute heart failure (HF). METHODS: We studied 209 patients with acute HF at an urban academic center and used ROC curves and multivariate analyses to examine the relationship of outcome to natriuretic peptide and cTnT concentrations at presentation. RESULTS: Higher concentrations of natriuretic peptides and cTnT at presentation were predictors of death at 60 days and 1 year (P <0.001 and P <0.01, respectively, at both time points). Optimal cutoff points for NT-proBNP, BNP, and cTnT for predicting death by 60 days or 1 year were 5562 and 3174 ng/L, 428 and 352 ng/L, and 0.01 and 0.01 microg/L, respectively. Most decedents demonstrated increased concentrations of both natriuretic peptides and cTnT and had a 25% mortality rate at the 60-day time point (P <0.001). Mortality rates were low (<4%) among patients with either no increase or an increase in only 1 marker. Decedents with increases in both a natriuretic peptide and cTnT at presentation had the highest death rate at 1 year (45%, P <0.001). This combination was strongly predictive of death [NT-proBNP plus cTnT: hazard ratio (HR), 7.66; 95% confidence interval (CI), 3.06-17.8; BNP plus cTnT: HR, 6.82; 95% CI, 2.99-16.5]. CONCLUSIONS: A dual-marker strategy incorporating a natriuretic peptide and cTnT is superior to either marker alone for estimating short- and longer-term risk in patients with acute HF.     

Abnormal rhythmic oscillations of atrial natriuretic peptide and brain natriuretic peptide in heart failure

The purpose of this study was to clarify whether the secretions of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are pulsatile in patients with chronic heart failure (CHF), and whether the rhythmic oscillations for ANP and BNP are abnormal in patients with CHF. Several reports have shown that ANP and especially BNP are valuable indicators of the prognosis in CHF. Previously, a pulsatile secretion has been described for ANP and BNP in healthy humans and for ANP in CHF patients. More information about the secretion pattern of BNP in heart failure is necessary to increase the clinical usefulness of BNP in patients with CHF. Patients with left ventricular systolic dysfunction and CHF ( n =12) and controls ( n =12) were investigated. Plasma ANP and BNP levels were determined every 2 min during a 2-h period by radioimmunoassay and analysed for pulsatile behaviour by Fourier transformation. All patients and controls had significant rhythmic oscillations in plasma ANP levels, and 11 patients with CHF and 10 controls had significant rhythmic oscillations in plasma BNP levels. The amplitude of the main frequency was considerably higher in patients with CHF than in controls (ANP: CHF, 4.76 pmol/l; controls, 0.75 pmol/l; P <0.01. BNP: CHF, 3.24 pmol/l; controls, 0.23 pmol/l; P <0.001; all values are medians), but the main frequency did not differ significantly between the group with CHF and the control group for either ANP or BNP. Patients with CHF demonstrate pulsatile secretion of ANP and BNP with a much higher absolute amplitude, but with the same main frequency as healthy subjects.     

脑钠肽前体及氨基末端脑钠肽前体基因的克隆与表达

目的在大肠杆菌中表达脑钠肽前体(proBNP)及氨基末端前体蛋白(NT-proBNP)。方法采用分子生物学技术构建重组质粒PGEX-20T-proBNP和PGEX-20T-NT-proBNP,分别对其进行PCR、双酶切和测序鉴定,然后将已测序鉴定的包含两种重组质粒的工程菌,转化至大肠杆菌BL21菌中表达脑钠肽前体及氨基末端前体蛋白,并用Western-blot鉴定纯化的重组蛋白。结果在大肠杆菌中成功的表达脑钠肽前体及氨基末端前体蛋白,两种蛋白均以可溶性形式表达,更有利于保存其生物学活性。结论两种蛋白的成功表达将有利于后续的单抗制备及检测试剂盒的开发奠定基础。