钠氢交换体1 mRNA在心力衰竭患者心肌组织中的表达及其与血浆内皮素的相关性研究

目的:观察钠氢交换体1(sodium-hydrogen exchanger 1,NHE-1)在心力衰竭(心衰)患者心肌组织中的表达及其与血浆内皮素的相关性,探讨NHE-1在心衰发生和发展中的作用及其机制。方法:采用实时荧光定量聚合酶链反应(FQ-PCR)检测35例心衰患者心肌组织中NHE-1mRNA的表达水平。采用放射免疫分析法测定受试者血浆内皮素-1(ET-1)含量,同时用心脏多普勒超声检查心脏左房内径、左室射血分数(LVEF)。研究NHE1mRNA在心衰患者心肌组织中的表达及其与血浆ET-1含量变化的相关性。结果:FQ-PCR检测心功能Ⅰ级组、心功能Ⅱ级组、心功能Ⅲ级组心衰患者心肌组织中NHE-1 mRNA的△Ct值分别为6.29±0.66、5.01±0.60、4.40±0.74。心功能Ⅱ级、心功能Ⅲ级组患者心肌组织中NHE-1 mRNA表达明显高于心功能Ⅰ级组(P0.01),心功能Ⅲ级组患者心肌组织中NHE-1 mRNA表达明显高于心功能Ⅱ级组(P0.05)。心衰组ET-1含量较对照组明显升高,并随心衰程度的加重而增加,心功能Ⅱ级组(P0.05)、心功能Ⅲ级组显著高于心功能Ⅰ级组(P0.05),心功能Ⅲ级组显著高于心功能Ⅱ级组(P0.05);且ET1含量与NHE-1 mRNA的△Ct值呈显著负相关。结论:心衰患者心肌组织中存在NHE-1 mRNA的高水平表达,血浆ET1含量显著增加,两者呈显著正相关。提示NHE-1及ET-1在心衰的发生和发展过程中可能起着重要作用。     

热休克蛋白47与PⅠCP在慢性心力衰竭患者中的相关性

目的:慢性心力衰竭（CHF）是一种慢性的,逐渐进展的临床综合征。研究热休克蛋白47(HSP47)与血清Ⅰ型胶原羧基端肽(PⅠCP)在CHF不同心功能分级中的表达及其相关性。方法: 将60名患者分为心功能Ⅰ级、心功能Ⅱ级、心功能Ⅲ级,采用ELISA测定患者血清中的HSP47的含量与PⅠCP的含量,并研究两者与CHF的相关性。结果: 与心功能1级组比较,心功能Ⅱ级组PⅠCP含量显著增高（P<0.01）,且心功能Ⅲ级组较心功能Ⅱ级组PⅠCP含量显著增高（P<0.01）,且血清HSP47含量与PⅠCP含量呈正相关。结论: CHF患者存在心肌纤维化及左心室扩大,两者呈正相关关系,提示CHF患者存在心室结构重构,心肌纤维化在心室重构中起重要作用。CHF患者HSP47和PⅠCP显著升高,且呈显著正相关。     

慢性缺氧大鼠心肌HSP47 mRNA的表达及其与PⅠCP和PⅢNP含量的相关性研究

目的探讨慢性缺氧大鼠心肌HSP47 mRNA表达与血清Ⅰ型前胶原C端原肽(PⅠCP)、Ⅲ型前胶原N端原肽(PⅢNP)含量及心肌纤维化的相关性。方法模拟缺氧环境,建立慢性缺氧大鼠模型。将40只SD大鼠随机分为5组,每组8只。对照组不给于缺氧处理(A组),各慢性缺氧组大鼠分别缺氧7 d(B组)、14 d(C组)、21 d(D组)、28 d(E组)。采用实时荧光定量PCR(q-PCR)检测心肌中热休克蛋白(HSP47)mRNA的表达量;运用酶联免疫吸附测定(ELISA)方法检测血清及心肌中PⅠCP、PⅢNP的浓度;采用HE和MASSON染色法对对照组和慢性缺氧组大鼠进行组织切片染色。结果与对照组比较,模型组的HSP47 mRNA表达量增多(P0.01),血清和心肌的PⅠCP、PⅢNP浓度升高(P0.01);心肌HSP417 mRNA的表达与血清和心肌的PⅠCP、PⅢNP含量呈正相关(P0.05);HE和MASSON染色显示慢性缺氧组心肌组织广泛纤维化。结论在慢性缺氧条件下HSP47 mRNA的表达量与PⅠCP、PⅢNP浓度正相关,提示HSP47作为心肌胶原分子伴侣在慢性缺氧所致心肌纤维化中起一定作用。     

Klotho基因在慢性心力衰竭患者心肌中的表达

目的探讨慢性心力衰竭(CHF)患者心肌组织中Klotho基因的表达及其与心肌纤维化的关系。方法心肌组织样本取材于2013年8月至2014年8月在成都军区昆明总医院心脏外科建立体外循环的60例CHF患者,按照纽约心脏联合会(NYHA)心功能分级将其分为:NYHAⅠ级组、Ⅱ级组、Ⅲ级组,每组患者各20例。运用实时荧光定量反转录-聚合酶链反应(RT-PCR)检测Klotho基因表达量,同时采用酶联免疫吸附测定(ELISA)方法检测上述60例患者血清中Ⅰ型C端胶原前肽(PⅠCP)的浓度。并对正常心肌组织及CHF患者心肌组织进行HE染色。结果(1)HE染色显示CHF患者心肌胶原增生;(2)与NYHAⅠ级组比较,Klotho基因在NYHAⅡ级、NYHAⅢ级组的心肌组织中表达明显减少(均P0.05),且在NYHAⅢ级组中的表达较NYHAⅡ级组明显减少(P0.05);(3)NYHAⅢ级组患者血清中PⅠCP的含量高于Ⅱ级、Ⅰ级组(均P0.05),NYHAⅡ级组高于Ⅰ级组(P0.05)。结论 CHF患者心肌组织Klotho基因的表达减少可能与随着心功能恶化,其抗衰老作用及抗心肌纤维化作用逐渐减弱有关。     

心房颤动患者衰老基因的表达及其与心肌纤维化的相关性

目的探讨心房颤动(简称房颤)患者KLOTHO基因的表达及其与纤维化的相关性。方法 60例行心脏手术患者按心脏节律分为窦性心律组、阵发性房颤组及持续性房颤动,每组20例。采用用实时荧光定量聚合酶链式反应的方法研究KLOTHO基因mRNA在患者心房肌组织中的表达,及其与血清中心肌纤维化指标Ⅰ型前胶原羧基端肽(PⅠCP)、Ⅲ型前胶原氨基端肽(PⅢNP)的关系。并行心肌组织切片HE染色来观察心肌纤维化的程度。结果①与窦性心律组相比,房颤组左房明显扩大(P0.05),持续性房颤组的左房内径大于阵发性房颤组(P0.05)。②与窦性心律组相比,阵发性房颤、持续性房颤组心房组织的KLOTHO mRNA水平均明显减少(P0.05);持续性房颤组KLOTHO mRNA表达较阵发性房颤组亦明显减少(P0.01)。③窦性心律组心肌间质中仅见极少量胶原纤维;阵发性房颤组心肌间质中胶原沉积增多,心肌肌束周围可见明显胶原纤维包绕;持续性房颤组心肌间质中纤维组织显著增生,心肌肌束被大量的条索状胶原纤维所分隔。④与窦性心律组相比,房颤组血清PⅠCP、PⅢNP含量明显增高(P0.01),且持续性房颤组PⅠCP、PⅢNP含量较阵发性房颤组明显增加(P0.05);⑤房颤患者心肌KLOTHO mRNA水平与左房内径、血清中PⅠCP、PⅢNP呈独立的、显著的负相关关系(P0.01)。结论房颤患者KLOTHO基因的表达增加,心肌纤维化的程度减少,提示KLOTHO基因可能与心房纤维化有关。     

螺内酯对老年人轻度心力衰竭心肌纤维化和心功能的影响

目的:探讨螺内酯对老年人轻度心力衰竭心肌纤维化和心功能的影响。方法:选择老年轻度心力衰竭患者(NYHA心功能分级为Ⅰ～Ⅱ级)67例为观察组,再随机分为常规治疗组(33例)和螺内酯组(34例);另健康对照组20例,治疗前和治疗3个月时采用放射免疫法测定血清Ⅲ型前胶原氨基半端肽(PⅢNP)和血浆脑钠肽(BNP)浓度,并应用心脏彩超测定心功能变化。结果:观察组血清PⅢNP和血浆BNP浓度均高于对照组(P<0.01);3个月后与治疗前比较:螺内酯组血PⅢNP和BNP均明显下降(P<0.01);且较常规治疗组亦明显下降(P<0.05,<0.01)。结论:在老年人轻度心力衰竭患者小剂量螺内酯治疗可以起到抗心肌纤维化、改善心功能的作用。     

螺内酯、氯沙坦对AMI大鼠血浆胶原代谢产物及心肌组织心钠素、醛固酮的影响

目的探讨螺内酯、氯沙坦对急性心肌梗死(AMI)大鼠血浆胶原代谢产物及心房利纳系统的影响。方法将AMI大鼠模型随机分成假手术组、AMI对照组、螺内酯组(S组)、氯沙坦组(L组)及合用组(S L组)。测定血浆Ⅲ型前氨基胶原末端肽(PⅢNP)、Ⅰ型前胶原羧基末端肽(PⅠ CP)、血浆和心肌血管紧张素Ⅱ(AngⅡ)、心钠素(ANP)、醛固酮(Ald)水平。结果①与AMI组比较,第2、6周L组、S组血浆PⅢNP、PⅠ CP均逐渐降低(P<0.05,P<0.01)。S组第2、6周血浆ANP逐渐下降(P<0.01);L组第2、6周血浆AngⅡ、ANP水平分别显著下降(P<0.01)。②与S及L组相比,S L各时间点血浆ANP均显著降低(P<0.01)。2与AMI组相比,第2、6周S组心肌ANP水平显著降低(P<0.01),L组与AMI组比、L组、S L组同S组相比,心肌AngⅡ、Ald和ANP均显著降低(P<0.01)。S L组与L组相比,心肌ANP显著降低(P<0.01)。结论螺内酯及氯沙坦可降低血浆PⅢNP、PⅠ CP和血浆、心肌组织ANP水平,二者联用有显著叠加效应。     

扩张型心肌病患儿血清PⅠCP、PⅢNP检测及意义

检测38例扩张型心肌病(DCM)患儿(观察组)和36例正常儿童(对照组)血清Ⅰ型、Ⅲ型前胶原羧基端肽(P Ⅰ CP,PⅢNP)水平,并用超声心动图行心功能检测.结果与对照组比较,观察组血清P Ⅰ CP、PⅢNP水平明显升高(P<0.05),心功能EF值、E/A显著降低(P均<0.05);血清P Ⅰ CP、PⅢNP水平与EF值、E/A值呈显著负相关(r分别为-0.79、-0.72、-0.77、-0.77,P均<0.01).认为血清PⅠCP、PⅢNP水平可用于评价DCM患儿心肌纤维化及心脏功能状况.     

Ⅰ、Ⅲ型前胶原端肽和血管紧张素Ⅱ与心功能不全的关系

目的　探讨Ⅰ型前胶原羧基端肽 (PⅠCP)、Ⅲ型前胶原氨基端肽 (PⅢNP)、血管紧张素Ⅱ (AⅡ )、醛固酮 (ALD)与心功能不全的关系。方法　采用ELISA法、放射免疫法对 5 1例充血性心力衰竭 (CHF)患者 (心功能Ⅱ级 14例 ,Ⅲ级 2 0例 ,Ⅳ级 17例 )血中PⅠCP、PⅢNP、AⅡ及ALD水平进行检测 ,并与 2 6名正常人 (对照组 )进行对比分析。结果　CHF患者血中PICP、PⅢNP、AⅡ及ALD水平较对照组明显增高 (P <0 .0 0 1) ,与病情的严重程度一致。相关分析表明 ,PⅠCP、PⅢNP分别与AⅡ、ALD呈正相关关系 (P <0 .0 5～ 0 .0 0 1)。结论　PⅠCP、PⅢNP可作为监测CHF患者心肌纤维化及进程的间接指标 ,反映CHF程度     

厄贝沙坦对慢性心力衰竭和心肌纤维化的影响研究

目的 探讨厄贝沙坦对心力衰竭患者心功能和心肌纤维化的影响.方法 选择心力衰竭患者（NYHA分级为Ⅱ～Ⅳ级）100例,随机分为常规治疗组和厄贝沙坦组.每组50例;在治疗前和治疗后12周应用心脏彩色超声测定心功能变化（测量LVEF）,采用放射免疫法检测血浆脑钠肽（BNP）、血清Ⅲ型前胶原氨基末端肽（PⅢNP）和透明质酸（HA）的浓度.结果 ①厄贝沙坦组BNP、PⅢNP和HA治疗后比常规治疗组治疗后降低效果更明显（P＜0.05）;两组患者LVEF值治疗后比治疗前明显升高（P＜0.01）,而且厄贝沙坦组治疗后与常规治疗组治疗后相比升高明显（P＜0.05）.②血清PⅢNP、HA与BNP值呈正相关,血清PⅢNP、HA与LVEF值呈负相关.结论 在常规治疗慢性心衰的基础上加用厄贝沙坦更能有效地抑制心脏HA和Ⅲ型胶原的产生,可以起到抗心肌纤维化、改善心功能的作用.     

急性心肌梗死经皮冠状动脉介入治疗患者心肌胶原与左心室重构的关系

目的探讨急性心肌梗死经皮冠状动脉介入(percutaneous coronary intervention,PCI)治疗患者心肌胶原变化与左心室重构关系。方法选择2011年12月至2012年9月入住宝安区人民医院的急性心肌梗死患者共70例为研究对象。按照入院后患者是否行直接PCI治疗分为直接PCI治疗组(n=30)和择期PCI治疗组(n=30),其中10例(其中直接PCI治疗组5例,择期PCI治疗组5例)患者出院后不愿意随访。所有入选患者术前、术后3 d及术后30 d均分别以酶联免疫吸附法测定血清Ⅰ型C端胶原前肽(carboxy-terminal propeptide of type I procollagen,PICP)、Ⅲ型N端胶原前肽(amino-terminal propeptide of type III procollagen,PⅢNP)和Ⅰ型C端胶原末肽(carboxy-terminal telopeptide of collagen type I,CITP)浓度;术后3 d、术后30 d均行心脏超声检查;术后30 d行单光子发射计算机断层显像测量心肌梗死面积。结果术后30 d直接PCI治疗组血清PICP、PⅢNP、CITP浓度较择期PCI治疗组明显降低,差异有统计学意义[PICP:(7.76±1.47)ng/mL vs.(10.73±1.67)ng/mL,P﹤0.05;PⅢNP:(11.17±4.72)ng/mL vs.(37.80±6.83)ng/mL,P﹤0.05;CITP:(31.18±6.78)ng/mL vs.(45.10±9.70)ng/mL,P﹤0.05]。术后30 d直接PCI治疗的左心室舒张末期内径、左心室收缩末期内径、心肌梗死面积明显低于择期PCI治疗组[(46.57±6.10)mm vs.(52.63±6.50)mm,P﹤0.05;(34.25±4.86)mm vs.(37.33±3.56)mm,P﹤0.05;22.8%±3.4%vs.28.2%±6.8%,P﹤0.05]。结论直接PCI治疗可有效地挽救濒死的心肌,减轻心室重构,保护心功能,改善患者远期预后。检测血清心肌胶原浓度能作为预测心室重构的指标。     

Role of sodium-hydrogen exchange in cardiac hypertrophy and heart failure: a novel and promising therapeutic target

The myocardial sodium-hydrogen exchanger (NHE), and more specifically the NHE-1 isoform is now well-recognized to be a major contributor to ischemic and reperfusion injury. Recent evidence suggests that NHE-1 is also potential candidate for targeted intervention in terms of attenuation of the remodelling and hypertrophic processes which contributes to heart failure. Experimental studies have shown that NHE-1 inhibitors attenuate cardiomyocyte hypertrophy induced by various factors and reduce heart failure in vivo, independently of infarct size reduction. Although the precise cellular mechanisms for NHE-1 involvement remain to be elucidated, current data suggest a potentially effective new therapeutic approach for the treatment of heart failure via NHE-1 inhibition. Received: 23 April 2001 / Accepted: 4 May 2001     

奥美沙坦对心肌梗死后心力衰竭大鼠内皮素1和肾上腺髓质素水平的影响

目的探讨奥美沙坦对心肌梗死后心力衰竭大鼠血浆内皮素1(endothelin-1,ET-1)、肾上腺髓质素(adrenomedullin,ADM)水平的影响。方法 Wistar大鼠38只,随机分为对照组10只、假手术组10只、模型组9只、奥美沙坦组9只。采用结扎大鼠冠状动脉左前降支的方法制作心肌梗死后心力衰竭模型,灌胃法给药8周。超声心动图检测用药前后大鼠心功能,放射免疫法测定血浆ET-1、ADM水平。结果用药前,对照组与假手术组大鼠LVEF、ET-1、ADM水平差异无统计学意义(P>0.05);与假手术组比较,模型组和奥美沙坦组大鼠LVEF明显降低,差异有统计学意义(P<0.01)。用药后,与假手术组比较,模型组大鼠ET 1、ADM水平明显升高,差异有统计学意义(P<0.05,P<0.01);与模型组比较,奥美沙坦组大鼠LVEF明显改善,ET-1、ADM水平明显降低,差异有统计学意义(P<0.05,P<0.01)。结论应用奥美沙坦治疗可以改善心肌梗死后心力衰竭大鼠心功能,降低心力衰竭时升高的血浆ET-1、ADM水平,抑制慢性心力衰竭时肾素-血管紧张素系统以外的神经内分泌系统激活,对慢性心力衰竭心脏起到保护作用。     

Transcardiac extraction of circulating endothelin-1 across the failing heart

To determine the transcardiac gradient of plasma endothelin-1 (ET-1) in patients with congestive heart failure (CHF), we measured plasma levels of ET-1 in both the aortic root and the coronary sinus in 14 normal subjects and 79 consecutive patients with CHF. In normal subjects, plasma ET-1 was significantly higher in the coronary sinus than in the aortic root; these findings were also shown in patients with mild CHF, suggesting that there was ET-1 spillover across the heart. In contrast, plasma ET-1 was significantly lower in the coronary sinus than in the aortic root in patients with severe CHF, suggesting there was ET-1 extraction across the heart in patients with severe CHF. The transcardiac gradient of plasma ET-1 was correlated with the left ventricular end-diastolic volume index (r = 0.501, p <0.0001) and plasma level of procollagen type III amino terminal peptide in the coronary sinus (r = 0.54, p = 0.0008), a marker of myocardial fibrosis. Stepwise multivariate analysis showed that the transcardiac gradient of plasma ET-1 was an independent and significant relation with the left ventricular end-diastolic volume index in patients with CHF (r = 0.665, p <0.0001). These findings suggest that elevated circulating ET-1 is extracted across the failing heart with a significant correlation between the transcardiac gradient of plasma ET-1 and the left ventricular end-diastolic volume index, suggesting that ET receptors are upregulated in the failing ventricle and that the elevated circulating ET-1 might stimulate the process of left ventricular remodeling in patients with severe CHF.     

Influence of primary coronary intervention on myocardial collagen metabolism and left ventricle remodeling predicted by collagen metabolism markers

The aims of the present study were to analyze cardiac collagen metabolism changes in vivo during acute and nonacute phases of ST elevation myocardial infarction (STEMI) in patients who were treated with primary coronary intervention (PCI) only, and to determine the predictive significance of collagen I and III synthesis markers (PICP, PIIINP) as well as the collagen I degradation marker (ICTP) on left ventricular function and volume changes after STEMI. Serum levels of the carboxy-terminal propeptide of type I procollagen (PICP) and amino-terminal propeptide of type III procollagen (PIIINP) assessed on the 30th day and the carboxyterminal telopeptide located at the C end of collagen type I (ICTP) assessed on the 7th day after STEMI were significantly higher (P = 0.01, P = 0.019, P = 0.04, respectively) in the PCI unsuccessful group than in the PCI successful group. These findings support the theory that early and successful PCI not only limits the amount of muscle necrosis but also protects cardiac collagen from ischemia-related injury. PICP and PIIINP levels assessed on the fourth day after acute STEMI enables us to predict the development of left ventricular function (EF) and end-diastolic volume changes over the course of 6 months, irrespective of the initial EF or revascularization success.     

Thrombolytic therapy with streptokinase stimulates collagen breakdown

BACKGROUND. Plasmin is capable of degrading extracellular matrix components such as collagen in vitro. To evaluate the significance of this for in vivo conditions, we set out to study the effect of streptokinase, which acts by converting plasminogen to plasmin, on the serum concentrations of the amino-terminal propeptide of type III procollagen (PIIINP) and the carboxy-terminal propeptide of type I procollagen (PICP). METHODS AND RESULTS. Twenty-three patients with suspected acute myocardial infarction were included in the study; 17 of them received thrombolytic therapy, and six were treated conservatively. PIIINP and PICP were assayed with radioimmunoassays. Kinetics of creatine kinase-MB release were determined to differentiate reperfusers from nonreperfusers. Composite curves of creatine kinase-MB release were constructed for different patient subgroups. During streptokinase infusion the serum concentrations of PIIINP increased rapidly, with a maximum mean increase of 50% (from 2.2 +/- 0.2 to 3.3 +/- 0.3 micrograms/l) in 45 minutes. A similar increase was also observed in two patients who received thrombolytic therapy but did not subsequently develop any myocardial infarction determined on the basis of enzyme release. The relative increase in PIIINP during streptokinase treatment was higher in those acute myocardial infarction patients with probable reperfusion than those with nonprobable reperfusion. Corresponding changes in PIIINP were not seen in the control group. Two days later there was a second increase in serum PIIINP for both patient groups. This change coincided with a similar increase in PICP. CONCLUSIONS. We conclude that streptokinase, probably by activation of plasminogen to plasmin, stimulates the breakdown of type III collagen during thrombolytic therapy. This phenomenon may decrease the risk of rethrombosis of the affected artery if the exposed collagen is responsible for thrombosis formation, but it could also be involved in the development of hemorrhagic complications during thrombolytic therapy. The second increase in PIIINP levels probably indicates type III collagen synthesis of the infarcted area. This investigation represents a pilot study, and more studies on the effects of various thrombolytic agents on interstitial collagen metabolism are obviously needed.     

Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure

OBJECTIVES: We sought to evaluate the effects of spironolactone on neurohumoral factors and left ventricular remodeling in patients with congestive heart failure (CHF). BACKGROUND: Aldosterone (ALD) promotes collagen synthesis and structural remodeling of the heart. Spironolactone, an ALD receptor antagonist, is reported to reduce mortality in patients with CHF, but its influence on left ventricular remodeling has not been clarified. METHODS: Thirty-seven patients with mild-to-moderate nonischemic CHF were randomly divided into two groups that received treatment with spironolactone (n = 20) or placebo (n = 17). We measured left ventricular volume and mass before treatment and after four months of treatment. We also measured the plasma levels of neurohumoral factors, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), as well as plasma procollagen type III aminoterminal peptide (PIIINP), a marker of myocardial fibrosis. RESULTS: Left ventricular volume and mass were significantly decreased and ejection fraction was significantly increased in the spironolactone group, while there were no changes in the placebo group. Plasma levels of ANP, BNP and PIIINP were significantly decreased after spironolactone treatment, but were unchanged in the placebo group. There was a significant positive correlation between the changes of PIIINP and changes of the left ventricular volume index (r = 0.45, p = 0.045) as well as the left ventricular mass index (r = 0.65, p = 0.0019) with spironolactone treatment. CONCLUSIONS: These findings indicate that four months of treatment with spironolactone improved the left ventricular volume and mass, as well as decreased plasma level of BNP, a biochemical marker of prognosis and/or ventricular hypertrophy, suggesting that endogenous aldosterone has an important role in the process of left ventricular remodeling in nonischemic patients with CHF.     

GDF-15与心肌梗死后心室重塑指标的相关性分析

目的：探讨心肌梗死后心力衰竭患者血清生长分化因子-15（GDF-15）水平的变化,及与心功能和心肌纤维化指标的相关性。方法：人选急性心肌梗死后心力衰竭患者100例为心衰组,健康体检者50例为健康对照组。检测并分析两组患者GDF-15水平的变化,及其与心功能[左心室收缩期内径（LVESd）、舒张末期内径（LVEDd）、左室射血分数（LVEF）]和心肌纤维化相关指标[脑钠肽（BNP）、血清转化生长因子（TGFp、I型前胶原氨基端肽（PINP）和Ⅲ型前胶原氨基端肽（PIIINP）]的相关性。结果：与健康对照组相比,心衰组血清GDF-15[（623．56±70．21）ng／L比（2003．53±163．2）ng／L]、TGFβ[（21．5±6．80）ng／ml比（58．93±12．81）ng／ml]、PINP[（150．58±32．57）ng／ml比（233．15±26．94）ng／ml]和PIIINP[（17．56±8．72）ng／ml比（48．64±9．28）ng／ml]明显升高（P〈0．05~〈0．01）。随着心功能分级的增加（Ⅱ-Ⅳ）,GDF-15的水平明显升高[（1521．32±98．23）ng／L比（2311．92±108．52）ng／L比（3023．54±129．36）ng／L,P均〈O．01]。Pearson相关分析结果显示,心肌梗死后心力衰竭患者血清GDF-15水平与LVEF呈负相关（r=-0．574,P〈O．05）,与LVESd和LVEDd呈正相关（r=0．688,0．752,P均〈0．05）;GDF-15水平与血浆BNP,血清PINP、PIIINP和TGFβ水平呈正相关（r=0．568～0．82,P均〈0．05）。结论：生长分化因子-15参与心肌梗死后心力衰竭患者的心室重塑。     

Early changes in serum markers of cardiac extra-cellular matrix turnover in patients with uncomplicated hypertension and type II diabetes

AIMS: Extracellular matrix (ECM) turnover is a major determinant of diastolic dysfunction and pumping capacity, thus potentially contributing to the progression of congestive heart failure (CHF). Patients with both arterial hypertension and diabetes have a high risk of heart failure. Whether these patients have changes in cardiac ECM has not been studied previously. Our objective was to compare blood markers of collagen turnover among patients with CHF, patients with hypertension and type II diabetes (HD), and healthy individuals. METHODS AND RESULTS: Measurements were performed in 239 CHF patients; 64 HD patients and 92 healthy subjects. We showed by adjusted ANOVA that PIIINP levels were significantly higher in CHF and HD patients than in controls, and higher in CHF patients than in HD patients. MMP1 levels were significantly lower in CHF and HD patients than in controls. Collagen type I markers (PICP and PINP) were not influenced by CHF but were lower in HD patients as compared to controls (p<0.05 for all comparisons). CONCLUSION: In heart failure, markers of cardiac collagen synthesis are increased and markers of degradation are decreased, potentially contributing to cardiac fibrosis and thus to poor outcome. Changes in collagen turnover may also occur early in the disease process in high-risk patients before heart failure is clinically detectable.