抗细胞因子治疗心力衰竭的研究进展

近年来 ,炎性细胞因子在心力衰竭发展中的作用已成为研究热点。有研究证实 ,抗细胞因子治疗可以减缓心力衰竭进程。因此 ,为了明确炎性细胞因子在心力衰竭病理生理发生机制中的作用 ,就以下几个方面作简要介绍 :炎性细胞因子的生物学特性及其对心脏重塑及心力衰竭发生发展的影响 ,目前抗细胞因子治疗心力衰竭策略的现状。     

β-受体阻滞剂在心力衰竭治疗中的应用

β-受体阻滞剂可以分为非选择性、选择性和具有血管扩张作用的β-受体阻滞剂3类。这类药物可以通过β信号系统上调、逆转重构、改善收缩和舒张功能、抗心律失常以及抗缺血等作用改善心力衰竭患者预后。随机对照临床研究已经证实其可以降低心力衰竭患者病死率、提高生存质量。各种指南也推荐其应用于心力衰竭的治疗。应用该类药物应该注意用药的时机、剂量、时程和禁忌证。     

螺内酯培哚普利与常规抗心力衰竭药物联用治疗心力衰竭的疗效观察

目的:观察螺内酯、培哚普利与常规抗心力衰竭药物联用治疗心力衰竭的疗效。方法:按入院顺序将82例心力衰竭患者均分为治疗组(螺内酯、培哚普利加常规抗心力衰竭药物)和对照组(培哚普利加常规抗心力衰竭药物),疗程2周。结果:治疗组心力衰竭总有效率88%,对照组为68%,2组比较差异有统计学意义(P<0·05)。结论:治疗组对心力衰竭疗效明显优于对照组。螺内酯、培哚普利与常规抗心力衰竭药物联用是一种较好的抗心力衰竭疗法。     

单核细胞趋化蛋白-1与心力衰竭

炎症是心力衰竭的重要组成部分.然而其导致心力衰竭发生、发展的详细机制仍不清楚.单核细胞趋化蛋白.1是引起慢性炎症的主要趋化因子并且在心力衰竭的发病学中起着重要作用.抗单核细胞趋化蛋白-1将是治疗心力衰竭极有希望的措施.     

抗心力衰竭治疗对充血性心力衰竭病人BNP及CA125的影响分析

目的探讨抗心力衰竭治疗对慢性充血性心力衰竭病人血清中脑利钠肽(BNP)以及糖类抗原125(CA125)的影响作用。方法选取2013年3月—2014年9月在我院接受治疗的慢性充血性心力衰竭病人50例,予抗心力衰竭治疗6周,分别于治疗前及治疗后对每位病人检测血清BNP及CA125进行,分析两项指标的变化。结果通过常规抗心力衰竭治疗6周后,病人血清中的BNP及CA125两项指标较治疗前明显下降(P0.05);予抗心力衰竭治疗前,病人BNP及CA125呈现正相关性(P0.05),病人心功能亦有显著改善。结论抗心力衰竭治疗能显著降低慢性充血性心力衰竭病人血清BNP及CA125水平,BNP与CA125可作为评价心力衰竭程度的指标。     

抗心律失常药在心力衰竭中的临床应用

医疗水平提升使心脏病患者的生存期延长,心力衰竭患病率亦呈上升趋势。心力衰竭患者常见并发心律失常,且发生心脏性猝死(SCD)的风险极高。如何防治心力衰竭,尤其是射血分数降低的心力衰竭(HFrEF)患者的心律失常及SCD,是临床面临的棘手问题。抗心律失常药的不良反应极大地限制了其在心力衰竭并心律失常中的临床应用,且药物防治SCD的作用极为有限。本文从临床角度,简述了近年来有关心力衰竭与心律失常的关联、抗心律失常药在心力衰竭临床应用的最新观点,为临床医师提供参考。     

心肌梗死后心力衰竭应用抗血小板聚集药物的展望

综述心肌梗死后心力衰竭抗血小板聚集药物的应用。长期的心肌损伤会导致心脏缺血、缺氧、心肌变性和纤维化,最终可导致心力衰竭。虽然抗心力衰竭手术治疗取得了突破性进展,但药物治疗仍是抗心力衰竭的基础。     

老年心力衰竭血清肿瘤坏死因子-α、白细胞介素-10、白细胞介素-4水平变化的临床研究

近年来研究表明，细胞因子参与了心力衰竭的发生、发展。炎症性细胞因子肿瘤坏死因子α（tumor necrosis factoralpha，TNF-α）和抗炎症性细胞因子白细胞介素-10（interleukin-10，IL-10）的失衡在心力衰竭中的作用和地位十分重要。而国内目前对其在老年心力衰竭中的作用研究不多。为此，本研究观察了不同心功能状态的老年心力衰竭患者血清TNF-α、IL-10和IL-4的浓度变化。     

氯沙坦对实验性高胆固醇血症兔动脉内膜的保护作用

肾素-血管紧张素系统(RAS)过度激活，与高血压、心力衰竭有关。氯沙坦是血管紧张素Ⅱ(AngⅡ)受体阻断剂，能从受体水平阻断RAS，发挥抗高血压、心力衰竭的作用，已被广泛运用于临床。我们通过兔高胆固醇血症诱导动脉粥样硬化模型．并用氯沙坦干预、以研究氯沙坦对血管内膜的保护作用及对AngⅡ、内皮素水平的影响．从而探讨氯沙坦抗动脉粥样硬化作用的有关机制。     

C型利钠肽与心力衰竭

C型利钠肽是利钠肽家族中的一员,高度保守,分布广泛,与心房利钠肽和脑利钠肽具有相似的结构和生理特性。C型利钠肽主要和利钠肽受体B结合,通过抗纤维化、抗过度增殖、抗过度肥大、抗炎症等生理效应在心血管疾病中发挥作用。心力衰竭时体内C型利钠肽的变化对疾病有预测意义,外源性C型利钠肽通过改善心脏功能对心力衰竭心脏起保护性作用。现就C型利钠肽的特征及其与心力衰竭的关系做一综述。     

Angiotensin-converting enzyme inhibition restores hepatocyte growth factor production in patients with congestive heart failure.

Endothelium-dependent vasodilation is impaired in patients with congestive heart failure. For vascular endothelium, hepatocyte growth factor (HGF) is one of the most potent and specific growth factors, which acts protectively against endothelial dysfunction. HGF production is downregulated by angiotensin II (Ang II) in vitro. We hypothesized that HGF production is impaired as the result of increased Ang II in patients with congestive heart failure, and that if so, the impaired production should be restored with angiotensin-converting enzyme inhibitors (ACE-I). We studied 16 patients with congestive heart failure caused by previous anterior myocardial infarction in whom left ventricular ejection fraction was 35+/-8% (mean+/-SD). Before and approximately 4 weeks after the treatment with ACE-I, blood samples were collected to measure the levels of HGF, Ang II, and brain natriuretic peptide as a biochemical marker for severity of heart failure. We also studied 5 control subjects, in whom heparin increased HGF production to 48+/-5-fold. However, in patients with heart failure, HGF response to heparin was significantly attenuated (24+/-5-fold, P<0.05 vs control). Therapy with ACE-I decreased the levels of Ang II and brain natriuretic peptide and restored HGF production in response to heparin by 43+/-7-fold, comparable to the control response. In conclusion, impaired HGF production was restored after the treatment with ACE-I probably by the mechanism of Ang II suppression. This novel effect of ACE-I may contribute to the clinical improvement in patients with heart failure and thereby may have an important therapeutic implication.     

扩张型心肌病伴心力衰竭患者肝细胞生长因子与心功能的相关性研究

目的 探讨扩张型心肌病伴心力衰竭患者血清肝细胞生长因子（HGF）浓度与心功能分级的关系.方法 纳入2011年至2013年扩张型心肌病伴心力衰竭患者63例作实验组,进一步按照NYHA心功能分级分为Ⅰ级组（n=15）、Ⅱ级组（n=16）、Ⅲ级组（n=15）和Ⅳ级组（n=17）,纳入同期健康志愿者32例作对照组.采用酶联免疫吸附法（ELISA）测定HGF浓度,电化学发光法测定血清N端脑钠肽前体（NT-proBNP）浓度,行心脏超声检查左心室舒张末期内径（LVEDD）和左心室射血分数（LVEF）,并采用线性回归分析血清HGF浓度和上述指标的相关性.结果 实验组各亚组的HGF浓度、NT-proBNP浓度、LVEDD值均高于对照组,差异有统计学意义（P＜0.05）,且心力衰竭程度越重,上述指标值越高,各组两两之间均存在统计学差异（P＜0.05）;实验组各亚组LVEF值均低于对照组,差异有统计学意义（P＜0.05）;血清HGF浓度与NT-proBNP浓度和LVEDD均呈正相关,相关系数分别为0.79和0.73,与LVEF值负相关,相关系数为-0.69（P均＜0.05）.结论 扩张型心肌病伴心功能不全患者血清HGF浓度和心功能不全的严重程度相关,对判断心功能不全严重程度有帮助.     

Hepatocyte growth factor: Effects on immune-mediated heart diseases

There is growing evidence of the potential role of hepatocyte growth factor (HGF) in various cardiovascular diseases. In addition to the beneficial effects of HGF in myocardial infarction, heart failure, and occlusive peripheral arterial disease, administration of HGF effectively suppresses acute and chronic cardiac allograft rejection and autoimmune myocarditis. The present review summarizes recent advances in the utility of HGF for heart diseases, especially immune-mediated heart diseases. Possible mechanisms of action in the suppression of T-cell-mediated immunity are also discussed.     

血清Periostin蛋白、肝细胞生长因子对慢性心衰患者心血管事件的预测价值

目的 探讨血清Periostin蛋白、肝细胞生长因子(hepatocyte growth factor,HGF)对慢性心力衰竭(chronic heart failure,CHF)的预测价值.方法 选取2018年1月至2019年3月我院收治的CHF患者(n=108),纳入同期体检健康者为对照组(n=50),采用ELIS...     

Circulating levels of hepatocyte growth factor and left ventricular remodelling after acute myocardial infarction (from the REVE-2 study)

Aim As experimental studies suggest that hepatocyte growth factor (HGF) is cardioprotective after myocardial infarction (MI), this study sought to investigate relationships between circulating levels of HGF and left ventricular (LV) remodelling in patients after acute MI. METHODS AND RESULTS: This prospective multicentre study included 246 patients with a first anterior Q-wave MI. Serial echocardiographic studies were performed at hospital discharge and 3 and 12 months after MI; quantitative analysis was performed at a core echocardiography laboratory. Blood samples to measure HGF, brain natriuretic peptide (BNP), and C-reactive protein were obtained at discharge and at the 1, 3, and 12 month follow-up visits. Plasma HGF levels were high at baseline, decreased at 1 month, and remained stable thereafter. In the post-MI period (at 3 and 12 months), HGF levels were positively associated with LV volumes, wall motion systolic index, E/Ea, and BNP; and negatively with LV ejection fraction. High HGF levels were associated with higher C-reactive protein levels. Multivariate analysis showed that both BNP (P < 0.0001) and C-reactive protein (P < 0.0001) were independently associated with HGF levels at 3 and 12 months. Patients who died or were rehospitalized for heart failure during follow-up had higher HGF levels at 1 month (P = 0.0006), 3 months (P = 0.018), and 1 year (P = 0.006) after MI. CONCLUSIONS: Circulating HGF levels correlate with all markers of LV remodelling after MI and are associated with rehospitalization for heart failure.     

Hepatocyte growth factor (HGF) in stable and unstable coronary heart disease

Hepatocyte growth factor (HGF) is an angiogenic factor upregulated in ischaemic diseases. We measured plasma HGF concentration in 26 patients (pts) with stable angina pectoris (SAP) and 16 pts with unstable angina pectoris (UAP). HGF levels were significantly higher in pts with UAP compared with pts with SAP (p<0,01), in pts with SAP vs control group (n=38, p<0,01) and in pts with UAP vs control group (p<0,001). HGF levels in SAP group correlated with heart failure symptoms (p=0,023). There was a trend towards significance between HGF and left ventricle ejection fraction (p=0,08) and between HGF and VEGF levels in pts with SAP (p=0,08). This study demonstrates that HGF plasma levels correlates with SAP symptoms. Pts with SAP and UAP has significantly higher levels of HGF comparing with control group.     

扩张型心肌病伴心衰患者肝细胞生长因子浓度与心功能的关系

目的探讨扩张型心肌病伴心衰患者血清肝细胞生长因子（HGF）浓度与心功能的关系。方法检测试验组扩张型心肌病伴心功能不全患者（NYHA心功能Ⅰ级15例、Ⅱ级16例、Ⅲ级15例、Ⅳ级17例）和26名健康对照者血清HGF浓度、NT—proBNP浓度、LVEDD值和LVEF值,比较各组各项指标的差异;同时探讨血清HGF浓度和上述指标的相关性。结果HGF浓度、NT—proBNP浓度、LVEDD值和LVEF值对照组分别为（323±29）pg／ml、（251±102）pg／ml、（42±7）mm和（57±11）％;NYHA心功能Ⅰ级组分别为（492±47）pg／ml、（973±112）pg／ml、（50±6）mm和（50±7）％;NYHA心功能Ⅱ级组分别为（607±68）pg／ml、（1229±214）pg／ml、（54±9）mm和（48±9）％;NYHA心功能Ⅲ级组分别为（662±94）pg／ml、（4208±1562）pg／ml、（59±16）mm和（42±7）％;NYHA心功能Ⅳ级组分别为（1028±135）pg／ml、（6963±2129）pg／ml、（66±19）mm和（38±6）％,各组间比较差异均有统计学意义（P〈0．05）.血清HGF浓度和NT—proBNP浓度呈正相关,相关系数为0．79;血清HGF浓度和LVEDD值呈正相关,相关系数为0．73;血清HGF浓度和LVEF值呈负相关,相关系数为-0．69。结论扩张型心肌病伴心功能不全患者血清HGF浓度和心功能不全的严重程度有关,可以作为心功能不全严重程度的预测因子。     

Prognostic Significance of Circulating Levels of Hepatocyte Growth Factor in Patients with Chagas' Disease and Idiopathic Dilated Cardiomyopathy

Objectives: Hepatocyte growth factor (HGF) plays an important role in the improvement in cardiac function and remodeling in a variety of cardiovascular diseases. It is also a strong predictor of mortality in some heart failure (HF) patients. However, its prognostic value in patients with Chagas' disease (CD) or idiopathic dilated cardiomyopathy (DCM) remains to be investigated. Methods and Results: In this prospective cohort study, HGF concentrations were measured in patients with CD (n = 91), DCM (n = 47), and control subjects (n = 25). While no difference was detected for patients with New York Heart Association class I-II, HGF was significantly increased in advanced HF patients (New York Heart Association class III-IV) in both CD and DCM groups, compared with healthy subjects. There was a strong correlation between HGF and left ventricular ejection fraction in CD patients. However, there was no correlation in patients with DCM. Despite its strong correlation with left ventricular ejection fraction in CD patients, HGF failed to predict mortality and necessity for heart transplant in both CD and DCM patients. Conclusions: Although HGF can be significantly increased in advanced HF patients with CD and DCM, its prognostic value for endpoints is minor. Therefore, the formerly described predictive power for HGF in HF might be restricted to specific etiologies of HF.     

Angiogenesis and antifibrotic action by hepatocyte growth factor in cardiomyopathy

Impairment of cardiac function in cardiomyopathy has been postulated to be related to decreased blood blow and increased collagen synthesis. Therefore, a therapeutic approach to alter the blood flow or fibrosis directly by means of growth factors may open a new therapeutic concept in dilated cardiomyopathy. From this viewpoint, hepatocyte growth factor (HGF) is a unique growth factor with antifibrosis and angiogenesis effects. Using the hereditary cardiomyopathic Syrian hamster as a model of genetically determined cardiomyopathy and heart failure, the effects of overexpression of HGF on fibrosis and microvascular dysfunction were examined. HGF gene or control vector was injected by the Hemagglutinating Virus of Japan-liposome method into the anterior heart of cardiomyopathic hamsters (Bio 14.6) under echocardiography once a week, from 12 to 20 weeks of age (total, 8 times). Blood flow, as assessed by a laser Doppler imager score, and the capillary density in hearts, as assessed by alkaline phosphatase staining, were significantly increased in hamsters transfected with HGF gene compared with control-vector-transfected hamsters (P<0.01). In contrast, the fibrotic area was significantly decreased in hamsters transfected with HGF gene compared with control (P<0.01). Overall, in vivo experiments demonstrated that transfection of HGF gene into the myocardium of cardiomyopathic hamsters stimulated blood flow through the induction of angiogenesis and reduction of fibrosis. These results suggest that HGF gene transfer may be useful to protect against myocardial injury in cardiomyopathy through its cardioprotective effects such as antifibrosis and angiogenesis actions.     

肝细胞生长因子治疗心肌梗死后心力衰竭的实验研究

目的研究经冠状动脉转染携带人肝细胞生长因子(hepatocytegrowthfactor,HGF)的腺病毒(adenovirus,Ad5)对猪心肌梗死后心力衰竭的改善作用。方法12只苏中幼猪,随机分成转染Ad5-HGF组(治疗组)和转染未携带肝细胞生长因子的腺病毒载体(null-Ad5)组(对照组),每组6只。结扎前降支制成心肌梗死模型,手术后第4周及第7周时行冠状动脉造影和门控心肌灌注显像,评价侧支循环形成程度(Rentorp法)、心肌灌注及心功能的变化;用ELISA法检测肝细胞生长因子蛋白表达;以免疫组织化学法检测基因导入后平滑肌肌动蛋白抗体阳性(SMA )有灌注功能血管生成情况。结果经冠状动脉转染Ad5-HGF后心肌高度表达人HGF蛋白;治疗组心肌血流灌注及左心室射血分数(LVEF)较对照组明显改善;治疗组侧支循环形成明显增多,每平方毫米功能血管的数量明显高于对照组。结论经冠状动脉转染Ad5-HGF能使心肌高度表达HGF蛋白。HGF对梗死心肌的侧支循环形成、心肌灌注及心功能均有改善作用,能促进功能血管数增多。