The Effects of Brain Natriuretic Peptide on Scar Formation in Incisional Rat Wounds

Background: Brain natriuretic peptide (BNP) is a peptide that reduces scar formation in the heart by blocking transforming growth factor‐β (TGF‐β). Although TGF‐β is known to play a role in scar formation in the myocardium, little is known about the effects of BNP on cutaneous wound healing. Objectives: The objective was to determine if the administration of BNP in healing cutaneous wounds reduces the amount of scarring. Methods: This was a laboratory investigation using 40 wild‐strain rats. Three full‐thickness 1‐cm incisional wounds were created on each animal and randomized to intradermal BNP, saline, or no treatment. Wounds were excised at 3, 7, 14, 31, and 60 days and examined histologically for scar surface area and collagen architecture. Those wounds excised at 30 days were subjected to a measure of tensile strength and those excised at 60 days were evaluated prior to excision for cosmesis using a scar evaluation scale. The proportion of wounds healing without visually apparent scar was the main outcome. Groups were compared with Fisher’s exact and Kruskal‐Wallis tests. Results: Wounds treated with BNP were more likely to heal without an apparent scar when compared to those treated with saline or control (37.5% vs. 0%, p = 0.03). There were no between‐group differences in the surface area of the scars or the collagen architecture. Incisional tensile strength was also similar across treatments. Conclusions: Treatment of rat incisions with BNP reduced the number of visually apparent scars but did not affect the histologic appearance of the scars or the incisional tensile strength.     

左西孟旦联合氢氯噻嗪治疗重症心力衰竭的临床研究

目的 探讨左西孟旦联合氢氯噻嗪治疗重症心力衰竭的临床疗效。方法 选取2020年7月—2023年7月复旦大学附属中山医院青浦分院重症监护室收治的100例重症心力衰竭患者，按随机数字法将所有患者分为对照组和治疗组，每组各50例。对照组患者口服氢氯噻嗪片，50 mg/次，2次/d。治疗组在对照组的治疗基础上静脉滴注左西孟旦注射液，5 mL加入5%葡萄糖注射液500 mL中。两组用药7 d。观察两组的临床疗效和临床症状改善时间，比较两组治疗前后心功能指标、生活质量综合评定问卷调查表（CQOLI-74）评分和血清细胞因子水平的变化情况。结果 治疗后，治疗组总有效率是98.0%，显著高于对照组的82.0%（P＜0.05）。治疗后，治疗组呼吸困难、乏力、气促、下肢水肿好转时间均短于对照组（P＜0.05）。治疗后，两组左室射血分数（LVEF）、心排血量（CO）、GQOLI-74评分均显著高于同组治疗前（P＜0.05）；治疗后，治疗组LVEF、CO、GQOLI-74评分高于对照组（P＜0.05）。治疗后，两组β型脑钠肽（BNP）、可溶性生长刺激表达基因2蛋白（sST2）、同型半胱氨酸（Hcy）、胱抑素C（CysC）水平均较同组治疗前显著降低（P＜0.05）；治疗后，治疗组BNP、sST2、Hcy、CysC水平低于对照组（P＜0.05）。结论 左西孟旦联合氢氯噻嗪治疗重症心力衰竭有较好的临床疗效，能有效改善患者的临床症状，增强心功能指标，降低机体炎性反应，值得临床借鉴应用。     

Human B-type natriuretic peptide is not degraded by meprin A

B-type natriuretic peptide (BNP) combats cardiac stress by reducing blood pressure and ventricular fibrosis. Human BNP is inactivated by unknown cell surface proteases. N-terminal cleavage of mouse BNP by the renal protease meprin A was reported to increase inactivating degradation by a second protease named neprilysin. Since the sequence surrounding the meprin A cleavage site in BNP differs between species, we tested whether meprin A degrades human BNP. Using a recently developed proteolytic bioassay, the ability of various protease inhibitors to block the inactivation of BNP was measured. In rat kidney membranes, inhibitors of meprin A or neprilysin partially or completely blocked inactivation of rat BNP_1-32 when added individually or in combination, respectively. In contrast, neither inhibitor alone or in combination prevented the inactivation of human BNP_1-32 by human kidney membranes. Leupeptin, a serine protease inhibitor, totally blocked inactivation of human BNP by human membranes, substantially blocked the inactivation of rat BNP_1-32 by human membranes, but had no effect on the inactivation of rat BNP_1-32 by rat kidney membranes. Purified neprilysin reduced the bioactivity of rat BNP_1-32 and human BNP. Digestion with both meprin and neprilysis caused the greatest reduction in rat BNP_1-32 but had no effect on the bioactivity of human BNP_1-32. We conclude that meprin A does not degrade BNP in humans and should not be considered a pharmacologic target of the natriuretic peptide system.     

血浆脑钠肽水平对冠心病诊断价值的初步探讨

目的通过检测观察冠心病患者血浆中脑钠肽(BNP)水平的改变,并与其肌钙蛋白I(cT n I)水平和高敏感性C反应蛋白(hs CRP)水平变化相比较,初步探讨将BNP作为冠心病临床诊断和治疗的标志物的可靠性。方法2004年3~11月,以分层随机抽样法获取西安地区健康人群血浆样本195份(男性132名,女性63名),西京医院住院患者血浆279份(包括129名冠心病、60名糖尿病、62名肺病疾患、28名单纯眼部疾患),利用微粒子酶免分析法和动态定时散射比浊法分别检测上述血浆BNP浓度、cT n I浓度及hs CRP浓度;将以上数据进行统计学分析,比较冠心病组与非冠心病组的差异显著性。结果统计学分析证实:冠心病组与正常组在BNP水平、cT n I水平及hs CRP水平上均存在非常显著性差异(P<0.01),而其中又以BNP水平差异显著性最大(P=0.001);糖尿病组、肺病组以及眼科阴性对照组的BNP浓度结果与正常组比较则显示无统计学意义(P>0.05)。结论血浆BNP浓度在冠心病患者中显著升高,进一步显示了其在心脏疾患中潜在的临床价值。     

脑钠肽对急诊呼吸困难的鉴别诊断价值

目的 评价快速测定脑钠肽(BNP)对充血性心力衰竭(CHF)所致呼吸困难的诊断价值。方法 测定152例以呼吸困难为主诉在急诊科就诊和急诊入院患者血浆BNP水平，以两位不知道BNP结果的心血管专家根据患者的临床资料作出的诊断为标准，来评价BNP水平在以呼吸困难为主诉的患者中诊断CHF的敏感性和特异性。结果 BNP≥100pg／mL诊断CHF的敏感性为96．3％，特异性为94．3％，阳性预测值为95．2％，阴性预测值为95．7％，阳性似然率和阴性似然率分别为16．9和0．038。BNP水平与心力衰竭的严重程度相关。结论 急诊快速测定BNP有助于鉴别心源性呼吸困难与非心源性呼吸困难。     

Using biomarkers to guide heart failure management

Introduction: Biomarkers have revolutionized the diagnosis of heart failure (HF), but it remains unclear how to use biomarkers to guide management of HF.

Areas covered: An exhaustive literature search on using biomarkers to guide HF management was performed. HF guidelines were carefully scrutinized for references pertaining to this topic, and Medline was employed to identify further references. This review focused on natriuretic peptides, troponin, and ST2 as biomarkers used to guide HF management. Most trials have examined secondary prevention of chronic HF patients, and data on primary prevention of HF and therapy of acute HF are emerging.

Expert commentary: While the current data on using biomarkers to guide HF management remain mixed, more research is necessary to better understand how to utilize biomarkers to improve HF management.     

血浆BNP变化与慢性心功能不全关系的研究

目的探讨血浆B型尿钠肽(BNP)与慢性心功能不全的关系。方法根据Framingham诊断标准纳入的50例慢性心功能不全患者,按NYHA分级,采用Triage快速定量测定仪检测BNP。结果从Ⅰ级～Ⅳ级各组患者,BNP水平逐渐升高;心功能Ⅳ级BNP水平高于心功能Ⅱ级组和Ⅲ级组(P均小于0.05);而心功能Ⅱ级、Ⅲ级和Ⅳ级组均高于心功能Ⅰ级组(P均小于0.05)。结论BNP将成为评价心脏功能状态的一个常规检查,成为慢性心功能不全的危险分层的指标。     

冠脉病变程度与脑钠肽的相关性研究

目的 研究非心衰冠心病患者冠脉病变程度与血浆脑钠肽(BNP)水平的相关关系及其临床意义.方法 选取浙江大学医学院附属第一医院心内科2007年3至5月住院的非心衰冠心病患者70例,符合冠心病临床诊断且冠脉造影结果阳性,将其分为三个组:稳定型心绞痛组24例,不稳定型心绞痛组25例,心肌梗死组21例.同时选取无冠心病病史且冠脉造影阴性者20例作为对照组.冠脉造影前用ELASA法测定各组血浆BNP浓度,冠脉造影后计算各组冠状动脉病变的支数和评分.比较冠心病各组与对照组的BNP水平,并将冠状动脉病变支数、评分与BNP水平作相关性分析.所得数据用SPSS 13.0统计软件处理,计量资料用均数±标准差(x±s)表示,显著性检验使用两个独立样本的非参数检验,以P＜0.01为差异具有统计学意义,相关分析选择spearman相关系数.结果 冠心病各组BNP水平均高于对照组,尤以心肌梗死组明显,与对照组之间比较差异具有统计学意义(P＜0.01).血浆BNP水平与冠状动脉病变支数、评分之间呈正相关关系,相关系数分别为r1=0.309、r2=0.279(P=0.01).结论 在排除心衰因素后,冠心病患者冠状动脉病变程度越重,BNP水平越高.冠状动脉病变所致的心肌缺血的严重程度与BNP水平相关,测定血浆BNP水平可对冠心病患者冠状动脉病变程度提供有价值的参考依据.     

B-型钠尿肽系列测定判定急性冠脉综合征患者预后的价值

目的探索对急性冠脉综合征（ACS）患者，B-型钠尿肽（BNP）系列测定联合TnT、CRP与不良心脏事件发生率的关系。方法对83例ACS患者分别在入院时、48h、72h测定其BNP、TnT、CRP值，以死亡、心肌梗死、症状性心衰为随访终点，平均随访12个月，对BNP等生化指标与心脏事件发生率的相关性进行统计学分析。结果随访中发现，BNP〉250ng／L的患者与BNP≤250ng／L的患者相比，心脏事件的发生率显著升高，为9％和27％（OR3．7，95％CI：2．3-5．7，P〈0．01）。在TnT阴性的患者，高BNP组与低BNP组相比，其危险比为5．9（95％CI2．6-13.3，P〈0．01）。在临床稳定、没有难治性心肌缺血的患者，BNP值快速下降，基线、48h、72h时的BNP值分别为248．6±10、188．9±8（-24％）、126．8±11（-49％），与基线相比，48h、72h差异均有统计学意义（P〈0．01）。BNP在基线时水平较低，而在72h显著升高的患者，预后较差，OR值为24．0（95％CI：8．4-32．5，P〈0．01）。而在基线时BNP值较高，72h时明显下降者，MACE发生率显著降低，与持续升高者相比，为16％vs38％（OR18．5，95％CI：7．6-21-3，P〈0．01）。结论对ACS患者，BNP是一个强有力的预后判断指标，并且BNP的系列测定与单一基线水平测定相比，其预后判断价值显著增加。