慢性充血性心力衰竭患者血粒细胞—巨噬细胞集落刺激因子含量的测定及临床意义
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摘要
目的：探讨慢性充血性心力衰竭(chronic congestive heart failure,C-HF)患者血粒细胞-巨噬细胞集落刺激因子(granulocyte-macrophage colo-ny stimulating factor,GM-CSF)含量及临床意义
方法：
1.选取我院心内科住院符合心力衰竭诊断及实验要求的CHF患者41例。其中男22例,女19例,年龄53-83(66.8±9.1)岁；正常对照组21例,为体检中心检查证实的健康人,其中男9例,女12例；年龄51-79(60.6±9.5)岁。排除标准：脑血管疾病、严重感染、近期有心肌梗死(6个月内)、肝及肾功能不全、恶性肿瘤、甲状腺疾病、糖尿病、血液及造血系统疾病者；近期(7天)内有以下引起心肌损伤标志物升高原因者：急性冠脉综合征、急性心力衰竭、心胸外科手术、胸外心脏按压、除颤、直流电复律者。
2.依据引起心力衰竭的病因分三组：风湿性心脏病组(13例),扩张型心肌病组(13例),冠心病组(15例)；三组年龄和性别差异无统计学意义(P>0.05)。将41例心力衰竭患者根据心力衰竭发生发展的过程,依据2001年美国心脏病学院／美国心脏学会(ACC/AHA)制定的标准分为两组：阶段C组(22例)和阶段D组(19例)；两组年龄和性别差异无统计学意义(P>0.05)。测定比较每组中GM-CSF的含量。
3.所有入选患者入院24小时内抽外周静脉血测定空腹血糖(FPG)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、肌酐(Cre),其中风湿性心脏病患者查类风湿因子,以上所有指标均在正常值范围之内；所有入选者在抽取上述空腹静脉血标本同时留取2毫升静脉血,离心后留取血清0.5毫升,放置-70℃冰箱保存,保存时间小于6个月。使用酶免免疫方法测定GM-CSF的浓度。
4.心脏彩超检查,提供左室内径(LVD)、左室舒张末直径(LVED)、左房内径(LAD)、左室射血分数(LVEF)数据,风湿性心脏病及扩张型心脏病均符合超声诊断标准。
5.统计学方法采用SPSS for windows 16.0软件包进行统计学分析,计量资料以均数±标准差表示,病例组和对照组间比较采用t检验,三组间及和对照组间差异显著性采用方差分析,P<0.05表示有统计学意义即有显著性差异。
结果：CHF组GM-CSF含量为85.50±76.20 pg／ml,正常对照组为26.05±8.55 pg／ml,CHF患者血GM-CSF含量显著高于正常对照组,两组间差异具有统计学意义(P<0.05)。风湿性心脏病组GM-CSF含量为153.85±104.50 pg／ml,扩张型心肌病组为58.25±20.33 pg／ml,冠心病组为49.87±22.10 pg／ml,风湿性心脏病组血清GM-CSF浓度最高,不仅显著高于正常对照组(P=0.005,P<0.05),而且高于扩张型心肌病(P=0.036,P<0.05)及冠心病组,有统计学意义(P=0.021,P<0.05)。但扩张型心肌病与冠心病两组间比较无统计学意义(P=0.873,P>0.05)。CHF阶段C组GM-CSF含量为53.91±22.22 pg／ml,CHF阶段D组GM-CSF含量为121.47±99.01 pg／ml,实验结果显示随着心力衰竭程度的逐渐加重,血GM-CSF含量明显升高,其差异具有统计学意义(P<0.05)。
结论：1.慢性充血性心力衰竭患者血清GM-CSF含量增高。增高的幅度与心力衰竭的严重程度有关,提示GM-CSF参与了慢性充血性心力衰竭的病理生理过程。2.不同病因的慢性充血性心力衰竭患者血清GM-CSF含量增高的程度不同。其中风湿性心脏病显著增高的结果提示血清GM-CSF含量可能与风湿免疫损伤密切相关。3.临床上测定血清GM-CSF含量有助于心力衰竭的鉴别诊断和心力衰竭严重程度的判断。
Objective:To investigate the content and significance of plasma granu-locyte-macrophage colony-stimulating factor in CHF.
Methods:
1.41 patients (male:22, female:19) with heart failure admitted into the cardiological department of our hospital were enrolled. Average age was 66.8±9.1 (53-83) years.21 healthy subjects (male:9, female:12) from the Health examining center were chosen as the control group, with an average age of 60.6±9.5 (51-79) years. Exclusion criteria:cerebrovascular disease, serious infection, recent (<6 months) myocardial infarction, liver and renal dysfunction, cancer, thyroid disease, diabetes, blood and hematopoietic system diseases. Moreover, those with diseases that may cause elevation of myocardial injury markers recently (7 days) were also excluded, including acute coronary syndrome, acute heart failure, heart surgery, closed chest cardiac compression, defibrillation, direct current cardioversion.
2. According to the etiology of heart failure, the subjects were divided into three groups:Rheumatic heart disease group (13cases), Dilated heart disease group (13cases) and Coronary heart disease group (15cases), there were no statistical significance among the there groups in age and sex (P >0.05). According to the criteria established by the American College of Cardiology/American Heart Association (ACC/AHA) in 2001, the subjects were divided into two groups:Stage C group and StageD group, considering the development of heart failure, there were no statistical significance among the two groups in age and sex (P>0.05). The content of GM-CSF in each group were determined.
3. Each subject underwent tests of fasting periphery venous blood within 24 hours by ELISA, including FPG,TG,TC,LDL-C,HDL-C and Creat-ine. Those with abnormal indicators were excluded.Meanwhile,each subject were subtract extra 2 ml venous blood.After centrifugation,0.5ml clear su-pernatant liquid were deserved in-70℃,less than 6 months.GM-CSF conc-entration was measured by ELISA.
4. Each subject underwent echocardiography. The diameters of LVED and LAD were measured by echocardiography. LVEF was determined by modified Simpson's method. Rheumatic heart disease and dilated heart disease met the corresponding diagnostic criteria.
5. Statistical analysis were conducted with SPSS 16.0 software. Quanti-titive data were expressed as means±standard deviation.Comparisons betwe-en the control and the patients'group were examined by t-test.Comparisons among the three groups and the control group were examined by ANOVA. P<0.05 was considered statistically significant.
Results:The serum level of GM-CSF in the CHF group was significan-tly higher than that in the control group (85.50±76.20 vs.26.05±8.55 pg/ml, P<0.05). The serum level of GM-CSF were 153.85±104.50 pg/ml in the rheumatic heart disease group,58.25±20.33 pg/ml in the dilated heart dise-ase group and 49.87±22.10 pg/ml in the coronary heart disease group.The serum level of GM-CSF in the rheumatic group was highest, comparing with the control group, the dilated heart disease and the CHD goup (P= 0.005, 0.036 and 0.021, respectively). There was no statistical significance betwe-en the dilated heart disease group and the coronary heart disease (P= 0.873, P> 0.05) group. Moreover, the serum level of GM-CSF was 53.91±22.22 pg/ml in CHF stage C group and was 121.47±99.01 pg/ml in CHF stage D group (P<0.05).
Conclusion:1.The level of serum GM-CSF increased in chronic conge-stive heart failure. The level of serum GM-CSF have certain relations with degree of heart failure. It was suggested that GM-CSF might take part in the pathophysiological process of CHF.2.The level of serum GM-CSF varied with differrent causes. Rheumatic heart disease was significantly higher and results suggest that the level of serum GM-CSF may be related to immunologic injury.3.Measurement of blood granulocyte-macrophage colony-stimulating factor may be useful in the diagnosis as well as the degree of heart failure.
方法：
1.选取我院心内科住院符合心力衰竭诊断及实验要求的CHF患者41例。其中男22例,女19例,年龄53-83(66.8±9.1)岁；正常对照组21例,为体检中心检查证实的健康人,其中男9例,女12例；年龄51-79(60.6±9.5)岁。排除标准：脑血管疾病、严重感染、近期有心肌梗死(6个月内)、肝及肾功能不全、恶性肿瘤、甲状腺疾病、糖尿病、血液及造血系统疾病者；近期(7天)内有以下引起心肌损伤标志物升高原因者：急性冠脉综合征、急性心力衰竭、心胸外科手术、胸外心脏按压、除颤、直流电复律者。
2.依据引起心力衰竭的病因分三组：风湿性心脏病组(13例),扩张型心肌病组(13例),冠心病组(15例)；三组年龄和性别差异无统计学意义(P>0.05)。将41例心力衰竭患者根据心力衰竭发生发展的过程,依据2001年美国心脏病学院／美国心脏学会(ACC/AHA)制定的标准分为两组：阶段C组(22例)和阶段D组(19例)；两组年龄和性别差异无统计学意义(P>0.05)。测定比较每组中GM-CSF的含量。
3.所有入选患者入院24小时内抽外周静脉血测定空腹血糖(FPG)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、肌酐(Cre),其中风湿性心脏病患者查类风湿因子,以上所有指标均在正常值范围之内；所有入选者在抽取上述空腹静脉血标本同时留取2毫升静脉血,离心后留取血清0.5毫升,放置-70℃冰箱保存,保存时间小于6个月。使用酶免免疫方法测定GM-CSF的浓度。
4.心脏彩超检查,提供左室内径(LVD)、左室舒张末直径(LVED)、左房内径(LAD)、左室射血分数(LVEF)数据,风湿性心脏病及扩张型心脏病均符合超声诊断标准。
5.统计学方法采用SPSS for windows 16.0软件包进行统计学分析,计量资料以均数±标准差表示,病例组和对照组间比较采用t检验,三组间及和对照组间差异显著性采用方差分析,P<0.05表示有统计学意义即有显著性差异。
结果：CHF组GM-CSF含量为85.50±76.20 pg／ml,正常对照组为26.05±8.55 pg／ml,CHF患者血GM-CSF含量显著高于正常对照组,两组间差异具有统计学意义(P<0.05)。风湿性心脏病组GM-CSF含量为153.85±104.50 pg／ml,扩张型心肌病组为58.25±20.33 pg／ml,冠心病组为49.87±22.10 pg／ml,风湿性心脏病组血清GM-CSF浓度最高,不仅显著高于正常对照组(P=0.005,P<0.05),而且高于扩张型心肌病(P=0.036,P<0.05)及冠心病组,有统计学意义(P=0.021,P<0.05)。但扩张型心肌病与冠心病两组间比较无统计学意义(P=0.873,P>0.05)。CHF阶段C组GM-CSF含量为53.91±22.22 pg／ml,CHF阶段D组GM-CSF含量为121.47±99.01 pg／ml,实验结果显示随着心力衰竭程度的逐渐加重,血GM-CSF含量明显升高,其差异具有统计学意义(P<0.05)。
结论：1.慢性充血性心力衰竭患者血清GM-CSF含量增高。增高的幅度与心力衰竭的严重程度有关,提示GM-CSF参与了慢性充血性心力衰竭的病理生理过程。2.不同病因的慢性充血性心力衰竭患者血清GM-CSF含量增高的程度不同。其中风湿性心脏病显著增高的结果提示血清GM-CSF含量可能与风湿免疫损伤密切相关。3.临床上测定血清GM-CSF含量有助于心力衰竭的鉴别诊断和心力衰竭严重程度的判断。
Objective:To investigate the content and significance of plasma granu-locyte-macrophage colony-stimulating factor in CHF.
Methods:
1.41 patients (male:22, female:19) with heart failure admitted into the cardiological department of our hospital were enrolled. Average age was 66.8±9.1 (53-83) years.21 healthy subjects (male:9, female:12) from the Health examining center were chosen as the control group, with an average age of 60.6±9.5 (51-79) years. Exclusion criteria:cerebrovascular disease, serious infection, recent (<6 months) myocardial infarction, liver and renal dysfunction, cancer, thyroid disease, diabetes, blood and hematopoietic system diseases. Moreover, those with diseases that may cause elevation of myocardial injury markers recently (7 days) were also excluded, including acute coronary syndrome, acute heart failure, heart surgery, closed chest cardiac compression, defibrillation, direct current cardioversion.
2. According to the etiology of heart failure, the subjects were divided into three groups:Rheumatic heart disease group (13cases), Dilated heart disease group (13cases) and Coronary heart disease group (15cases), there were no statistical significance among the there groups in age and sex (P >0.05). According to the criteria established by the American College of Cardiology/American Heart Association (ACC/AHA) in 2001, the subjects were divided into two groups:Stage C group and StageD group, considering the development of heart failure, there were no statistical significance among the two groups in age and sex (P>0.05). The content of GM-CSF in each group were determined.
3. Each subject underwent tests of fasting periphery venous blood within 24 hours by ELISA, including FPG,TG,TC,LDL-C,HDL-C and Creat-ine. Those with abnormal indicators were excluded.Meanwhile,each subject were subtract extra 2 ml venous blood.After centrifugation,0.5ml clear su-pernatant liquid were deserved in-70℃,less than 6 months.GM-CSF conc-entration was measured by ELISA.
4. Each subject underwent echocardiography. The diameters of LVED and LAD were measured by echocardiography. LVEF was determined by modified Simpson's method. Rheumatic heart disease and dilated heart disease met the corresponding diagnostic criteria.
5. Statistical analysis were conducted with SPSS 16.0 software. Quanti-titive data were expressed as means±standard deviation.Comparisons betwe-en the control and the patients'group were examined by t-test.Comparisons among the three groups and the control group were examined by ANOVA. P<0.05 was considered statistically significant.
Results:The serum level of GM-CSF in the CHF group was significan-tly higher than that in the control group (85.50±76.20 vs.26.05±8.55 pg/ml, P<0.05). The serum level of GM-CSF were 153.85±104.50 pg/ml in the rheumatic heart disease group,58.25±20.33 pg/ml in the dilated heart dise-ase group and 49.87±22.10 pg/ml in the coronary heart disease group.The serum level of GM-CSF in the rheumatic group was highest, comparing with the control group, the dilated heart disease and the CHD goup (P= 0.005, 0.036 and 0.021, respectively). There was no statistical significance betwe-en the dilated heart disease group and the coronary heart disease (P= 0.873, P> 0.05) group. Moreover, the serum level of GM-CSF was 53.91±22.22 pg/ml in CHF stage C group and was 121.47±99.01 pg/ml in CHF stage D group (P<0.05).
Conclusion:1.The level of serum GM-CSF increased in chronic conge-stive heart failure. The level of serum GM-CSF have certain relations with degree of heart failure. It was suggested that GM-CSF might take part in the pathophysiological process of CHF.2.The level of serum GM-CSF varied with differrent causes. Rheumatic heart disease was significantly higher and results suggest that the level of serum GM-CSF may be related to immunologic injury.3.Measurement of blood granulocyte-macrophage colony-stimulating factor may be useful in the diagnosis as well as the degree of heart failure.
引文
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38. Hohensinner PJ, Rychli K, Zorn G, et al. Macrophage-modulating cytokines predict adverse outcome in heart failure, Thromb Haemost 2010 Feb;103 (2):435-41.
39. Loredana Postiglione, Stefania Montagnani, Paolo Ladogana, et al. Granulocyte Macrophage-Colony Stimulating Factor receptor expression on human cardio-myocytes from end-stage heart failure patient, European Journal of Heart Failure 2006;9:564-70.
40. Woo YJ, Grand TJ, Berry MF, et al. Stromal cell-derived factor and granul-ocyte-monocyte colony-stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy, J Thorac Cardiovasc Surg 2005; 130 (2):21-329.
41. Joseph J, RimawiA, Mehta P,et al. Safety and effectiveness of granulocyte colony stimulating factor in mobilizing stem cells and improving cytokine prof-
ile in advanced chronic heart failure, Am J Cardiol 2006;97(5):681-4.
42. Doyle SE, Gasson JC. Characterization of the role of the human Granulocyte Macrophage-Colony Stimulating Factor receptor a subunit in the activation of JAK 2 and STAT 5, Blood 1998;92:867-76.
43. Genth-Zotz S,Bolger AP,Kalra PR,et al.Heat shock 70 in patients with chronic heart failure:relation to disease severity and survival,Int J Cardiol 2004;96(3): 397-401.
44. Anversa P, Kajstura J. Ventricular myocytes are not terminally differentiated in the adult mammalian heart, Circ Res 1998;83(1):1-14.
45. Kajstura J, Leri A, Finato N, et al. Myocyte proliferation in end-stage cardiac failure in humans, Med Sci 1998;95(15):8801-80.
46. Beltrami AP, Urbanek K, Kajstura J, et al. Evidence that human cardiac myocyte divide after myocardial infarction, N Engl J Med 2000;344(23):1750-7.
47. Beltrami CA, Di Loreto C, Finato N, et al. Proliferating cell nuclear antigen (PCNA), DNA synthesis and mitosis in myocytes following cardiac transplant-tation in man, J Mol Cell Cardiol 1998;29(10):2789-802.
1. 中华医学会心血管病分学会,中华心血管病杂志编辑委员会.慢性心力衰竭诊断治疗指南.中华心血管病杂志,2007,35(12)：1076.
2. 赵水平,胡大一.心血管病诊疗指南解读.第3版.北京：人民卫生出版社,2008.
3. Colucci WS. Molecular and cellular mechanisms of myocardial failure, Am J Cardiol 1997;80(11):15-25.
4. Rondini G, Chirico G. Hematopoietic growth factor levels in term and preterm infants[J], Curr Opin Hematol 1999;6:192-7.
5. Hunt SA, Abraham WT, Chin MH,et al. ACC/AHA 2005 Guideline Update for the diagnosis and Management of Chronic Heart Failure in the Adult:a report of the Americn College of Cardiology/American Heart Association Task Force on practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure):developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation:endorsed by the Heart Rhythm Society, Circulation 2005;112(12):154-235.
6. 兰海霞,陈志英,张建清.粒细胞-巨噬细胞集落刺激因子在呼吸道感染患儿血清中的变化.华北国防医药,2004,16(6)：389-390.
7. Parissis JT, Adamopoulos S, Venetsanou K, et al. Plasma profiles of circulating granulocyte-macrophage colony-stimulating factor and soluble cellular adhesion molecules in acute myocardial infarction. Contribution to post-infarction left ventricular dysfunction. Eur Cytokine Netw 2004 Apr-Jun;15(2):139-44.
8. Parissis JT, Adamopoulos S, Venetsanou KF, et al. Clinical and neurohormonal correlates of circulating granulocyte-macrophage colony-stimulating factor in severe heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 2000;86(6):707-10.
9. Loredana Postiglione, Stefania Montagnani, Paolo Ladogana, et al.Granulocyte Macrophage-Colony Stimulating Factor receptor expression on human cardiomy-ocytes from end-stage heart failure patients. European Journal of Heart Failure, 2006 Feb;9:564-70.
10. Kohno Y, Tanimoto A, Cirathaworn C, et al. GM-CSF activates RhoA.integrin and MMP expression in human monocytic cells. Pathol Int 2004;54:693-702.
11.徐灵敏,安金斗,刘松茂,等.小儿心肌疾病抗ADP/ATP载体抗体与粒细胞-
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12.王婧岚,李艳,胡素君,等.心力衰竭患儿粒细胞-巨噬细胞集落刺激因子含量变化及意义.河南医药信息,2001；9(5)：13.
13. Hwang S, Harris TJ, Wilson NW,et al. Immune function in patients with chronic stable-congestive heart failure, American Heart Journal 1992; 125:1651.
14. Shusaku Miyata, Genzou Takemura, Yukinori Kawase, et al. Autophagic Card-iomyocyte Death in Cardiomyopathic Hamsters and Its Prevention by Granulo-cyte Colony-Stimulating Factor, American Journal of Pathology 2006; 168 (2):386-97.
15. Hohensinner PJ, Rychli K, Zorn G, et al. Macrophage-modulating cytokines predict adverse outcome in heart failure, Thromb Haemost 2010Feb;103(2): 435-41.
16. Anversa P, Kajstura J. Ventricular myocytes are not terminally differentiated in the adult mammalian heart, Circ Res 1998;83(1):1-14.
17. Kajstura J, Leri A, Finato N, et al. Myocyte proliferation in end-stage cardiac failure in humans, Med Sci 1998;95(15):8801-80.
18. Beltrami AP, Urbanek K, Kajstura J, et al. Evidence that human cardiac myocyte divide after myocardial infarction, N Engl J Med 2000;344(23):1750-7.
19. Beltrami CA, Di Loreto C, Finato N, et al. Proliferating cell nuclear antigen (PCNA), DNA synthesis and mitosis in myocytes following cardiac transplantation in man, J Mol Cell Cardiol 1998;29(10):2789-802.
20. Seiler C, Pohl T, Wustmann K, et al. Promotion of collateral growth by granu-locyte macrophage colony-stimulating factor in patientswith coronary artery disease:a randomized, double-blind, placebo controlled study[J], Circulation 2001;104(17):2012-7.
21. Woo YJ, Grand TJ, Berry MF, et al. Stromal cell-derived factor and granulocyte-monocyte colony-stimulating factor form a combined neovasculog-enic therapy for ischemic cardiomyopathy, J Thorac Cardiovasc Surg 2005; 130 (2):321-29.
22. li Y, Takemura G, Okada H,et al. Treatment with granulocyte colony stimulating factor am eliorates chronic heart failure[J], Lab Invest 2006;86(1):32-44.
23. Joseph J, Rimawi A, Mehta P, et al.Safety and effectiveness of granulo-cyte-colony stimulating factor in m obilizing stem cells and im proving cytokine profile in advanced chronic heart failure[J], Am J Cardiol 2006;97(5):681-4
24. Terrovitis J, Charitos C, Dolou P, et al. No effect of stem cellmobilization with GM-CSF on infarct size and left ventricular function in experimental acute myocardial infarction [J], B asic Res Cardiol 2004;99(4):241-6.
25. Maekawa Y, Anzai T, Yoshikawa T, et al. Effect of granulocyte macrophage colony-stimulating factor inducer on left ventricular remodeling after acute myocardial infarction[J], J Am Coll Cardiol 2004;44(7):1510-20.
26. Kass E,Parker J,Schlom, et al. Comparative studies of the effects of recombiant GM-CSF and GM-CSF administered via a poxvirus to enhance the concentration of antigen presenting cells in regional lymphnodes[J], Cytokine 2000; 12(7):960.
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30. Doyle SE, Gasson JC. Characterization of the role of the human Granulocyte Macrophage-Colony Stimulating Factor receptor a subunit in the activation of JAK 2 and STAT 5, Blood 1998;92:867-76.
31. Genth-Zotz S, Bolger AP, Kalra PR, et al. Heat shock 70 in patients with chronic heart failure:relation to disease severity and survival, Int J Cardiol 200-4;96(3):397-401.
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8. Hohensinner PJ, Rychli K, Zorn G, et al. Macrophage-modulating cytokines predict adverse outcome in heart failure, Thromb Haemost 2010 Feb;103(2): 435-41.
9. Loredana Postiglione, Stefania Montagnani, Paolo Ladogana, et al. Granulocyte Macrophage-Colony Stimulating Factor receptor expression on human cardiom-yocytes from end-stage heart failure patient, European Journal of Heart Failure 2006;9:564-70.
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14. Kalka C, Masuda H, Takahashi T, et al.Transplantation of exvivo expanded endothelial progenitor cells for therapeutic neovascularization[J], Proc Natl Ac-ad Sci USA 2000;97:3422.
15. Hwang S, Harris TJ, Wilson NW,et al. Immune function in patients with chronic stable-congestive heart failure, American Heart Journal 1992; 125:1651.
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36.赵水平,胡大一.心血管病诊疗指南解读.第3版.北京人民卫生出版社,2008.
37 Colucci WS. Molecular and cellular mechanisms of myocardial failure, Am J Ca-rdiol 1997;80(11):15-25.
38. Hohensinner PJ, Rychli K, Zorn G, et al. Macrophage-modulating cytokines predict adverse outcome in heart failure, Thromb Haemost 2010 Feb;103 (2):435-41.
39. Loredana Postiglione, Stefania Montagnani, Paolo Ladogana, et al. Granulocyte Macrophage-Colony Stimulating Factor receptor expression on human cardio-myocytes from end-stage heart failure patient, European Journal of Heart Failure 2006;9:564-70.
40. Woo YJ, Grand TJ, Berry MF, et al. Stromal cell-derived factor and granul-ocyte-monocyte colony-stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy, J Thorac Cardiovasc Surg 2005; 130 (2):21-329.
41. Joseph J, RimawiA, Mehta P,et al. Safety and effectiveness of granulocyte colony stimulating factor in mobilizing stem cells and improving cytokine prof-
ile in advanced chronic heart failure, Am J Cardiol 2006;97(5):681-4.
42. Doyle SE, Gasson JC. Characterization of the role of the human Granulocyte Macrophage-Colony Stimulating Factor receptor a subunit in the activation of JAK 2 and STAT 5, Blood 1998;92:867-76.
43. Genth-Zotz S,Bolger AP,Kalra PR,et al.Heat shock 70 in patients with chronic heart failure:relation to disease severity and survival,Int J Cardiol 2004;96(3): 397-401.
44. Anversa P, Kajstura J. Ventricular myocytes are not terminally differentiated in the adult mammalian heart, Circ Res 1998;83(1):1-14.
45. Kajstura J, Leri A, Finato N, et al. Myocyte proliferation in end-stage cardiac failure in humans, Med Sci 1998;95(15):8801-80.
46. Beltrami AP, Urbanek K, Kajstura J, et al. Evidence that human cardiac myocyte divide after myocardial infarction, N Engl J Med 2000;344(23):1750-7.
47. Beltrami CA, Di Loreto C, Finato N, et al. Proliferating cell nuclear antigen (PCNA), DNA synthesis and mitosis in myocytes following cardiac transplant-tation in man, J Mol Cell Cardiol 1998;29(10):2789-802.
1. 中华医学会心血管病分学会,中华心血管病杂志编辑委员会.慢性心力衰竭诊断治疗指南.中华心血管病杂志,2007,35(12)：1076.
2. 赵水平,胡大一.心血管病诊疗指南解读.第3版.北京：人民卫生出版社,2008.
3. Colucci WS. Molecular and cellular mechanisms of myocardial failure, Am J Cardiol 1997;80(11):15-25.
4. Rondini G, Chirico G. Hematopoietic growth factor levels in term and preterm infants[J], Curr Opin Hematol 1999;6:192-7.
5. Hunt SA, Abraham WT, Chin MH,et al. ACC/AHA 2005 Guideline Update for the diagnosis and Management of Chronic Heart Failure in the Adult:a report of the Americn College of Cardiology/American Heart Association Task Force on practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure):developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation:endorsed by the Heart Rhythm Society, Circulation 2005;112(12):154-235.
6. 兰海霞,陈志英,张建清.粒细胞-巨噬细胞集落刺激因子在呼吸道感染患儿血清中的变化.华北国防医药,2004,16(6)：389-390.
7. Parissis JT, Adamopoulos S, Venetsanou K, et al. Plasma profiles of circulating granulocyte-macrophage colony-stimulating factor and soluble cellular adhesion molecules in acute myocardial infarction. Contribution to post-infarction left ventricular dysfunction. Eur Cytokine Netw 2004 Apr-Jun;15(2):139-44.
8. Parissis JT, Adamopoulos S, Venetsanou KF, et al. Clinical and neurohormonal correlates of circulating granulocyte-macrophage colony-stimulating factor in severe heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 2000;86(6):707-10.
9. Loredana Postiglione, Stefania Montagnani, Paolo Ladogana, et al.Granulocyte Macrophage-Colony Stimulating Factor receptor expression on human cardiomy-ocytes from end-stage heart failure patients. European Journal of Heart Failure, 2006 Feb;9:564-70.
10. Kohno Y, Tanimoto A, Cirathaworn C, et al. GM-CSF activates RhoA.integrin and MMP expression in human monocytic cells. Pathol Int 2004;54:693-702.
11.徐灵敏,安金斗,刘松茂,等.小儿心肌疾病抗ADP/ATP载体抗体与粒细胞-
巨噬细胞集落刺激因子的临床研究.中华儿科杂志,1998；36(5)：276.
12.王婧岚,李艳,胡素君,等.心力衰竭患儿粒细胞-巨噬细胞集落刺激因子含量变化及意义.河南医药信息,2001；9(5)：13.
13. Hwang S, Harris TJ, Wilson NW,et al. Immune function in patients with chronic stable-congestive heart failure, American Heart Journal 1992; 125:1651.
14. Shusaku Miyata, Genzou Takemura, Yukinori Kawase, et al. Autophagic Card-iomyocyte Death in Cardiomyopathic Hamsters and Its Prevention by Granulo-cyte Colony-Stimulating Factor, American Journal of Pathology 2006; 168 (2):386-97.
15. Hohensinner PJ, Rychli K, Zorn G, et al. Macrophage-modulating cytokines predict adverse outcome in heart failure, Thromb Haemost 2010Feb;103(2): 435-41.
16. Anversa P, Kajstura J. Ventricular myocytes are not terminally differentiated in the adult mammalian heart, Circ Res 1998;83(1):1-14.
17. Kajstura J, Leri A, Finato N, et al. Myocyte proliferation in end-stage cardiac failure in humans, Med Sci 1998;95(15):8801-80.
18. Beltrami AP, Urbanek K, Kajstura J, et al. Evidence that human cardiac myocyte divide after myocardial infarction, N Engl J Med 2000;344(23):1750-7.
19. Beltrami CA, Di Loreto C, Finato N, et al. Proliferating cell nuclear antigen (PCNA), DNA synthesis and mitosis in myocytes following cardiac transplantation in man, J Mol Cell Cardiol 1998;29(10):2789-802.
20. Seiler C, Pohl T, Wustmann K, et al. Promotion of collateral growth by granu-locyte macrophage colony-stimulating factor in patientswith coronary artery disease:a randomized, double-blind, placebo controlled study[J], Circulation 2001;104(17):2012-7.
21. Woo YJ, Grand TJ, Berry MF, et al. Stromal cell-derived factor and granulocyte-monocyte colony-stimulating factor form a combined neovasculog-enic therapy for ischemic cardiomyopathy, J Thorac Cardiovasc Surg 2005; 130 (2):321-29.
22. li Y, Takemura G, Okada H,et al. Treatment with granulocyte colony stimulating factor am eliorates chronic heart failure[J], Lab Invest 2006;86(1):32-44.
23. Joseph J, Rimawi A, Mehta P, et al.Safety and effectiveness of granulo-cyte-colony stimulating factor in m obilizing stem cells and im proving cytokine profile in advanced chronic heart failure[J], Am J Cardiol 2006;97(5):681-4
24. Terrovitis J, Charitos C, Dolou P, et al. No effect of stem cellmobilization with GM-CSF on infarct size and left ventricular function in experimental acute myocardial infarction [J], B asic Res Cardiol 2004;99(4):241-6.
25. Maekawa Y, Anzai T, Yoshikawa T, et al. Effect of granulocyte macrophage colony-stimulating factor inducer on left ventricular remodeling after acute myocardial infarction[J], J Am Coll Cardiol 2004;44(7):1510-20.
26. Kass E,Parker J,Schlom, et al. Comparative studies of the effects of recombiant GM-CSF and GM-CSF administered via a poxvirus to enhance the concentration of antigen presenting cells in regional lymphnodes[J], Cytokine 2000; 12(7):960.
27. Asahara T, Masuda H. Bone marroworigin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization[J], Circ Res 1999;85:221.
28. Murohara T, Ikeda H, Duan J. Transplanted cord brood-derived endothelial precursor cells augment postnatal neovascularization [J], J ClinInvest 2000; 105:1527
29. Kalka C, Masuda H, Takahashi T, et al. Transplantation of exvivo expanded end-othelial progenitor cells for therapeutic neovascularization[J], Proc Natl Acad Sci USA 2000;97:3422.
30. Doyle SE, Gasson JC. Characterization of the role of the human Granulocyte Macrophage-Colony Stimulating Factor receptor a subunit in the activation of JAK 2 and STAT 5, Blood 1998;92:867-76.
31. Genth-Zotz S, Bolger AP, Kalra PR, et al. Heat shock 70 in patients with chronic heart failure:relation to disease severity and survival, Int J Cardiol 200-4;96(3):397-401.