粒细胞集落刺激因子与心血管疾病

近年来大量的研究表明骨髓干细胞能够促进心肌梗死后侧支循环的形成,加快血管损伤后内皮的修复.粒细胞集落刺激因子是一类血液生长因子,近来研究发现它可以动员骨髓干细胞,使它们归巢到梗死区域,复制、分化并促进心肌的修复.本文就粒细胞集落刺激因子在心血管疾病,包括心肌梗死、血管损伤后再狭窄和心力衰竭中的作用机制及应用进行综述.     

粒细胞集落刺激因子治疗急性脑梗死的临床研究

目的:探讨粒细胞集落刺激因子(G CSF)治疗急性脑梗死的疗效和安全性。方法:74例急性脑梗死患者随机分为治疗组和对照组。对照组按急性脑梗死常规方法治疗,治疗组在常规治疗基础上加用G CSF。两组病例于治疗前、治疗后1个月和3个月时分别进行Barthel指数(BI)和中国卒中量表(CSS)评定,并观察G CSF治疗期间的不良反应和随访末期的死亡/残障率。结果:71例完成了3个月的观察。治疗组无死亡病例,失访1例;对照组死亡2例。两组治疗后1个月BI和CSS评分即有所改善,但两组差异无显著意义;治疗后3个月,治疗组BI和CSS评分均优于对照组(P<0.01)。治疗组随访末期死亡/残障率为57%,低于对照组的78%(P<0.05)。G CSF治疗期间未出现明显不良反应。结论:G CSF治疗急性脑梗死安全易行,且能改善3个月时的神经功能和预后。     

粒细胞集落刺激因子治疗心肌梗死

粒细胞集落刺激因子治疗心肌梗死,能动员骨髓干细胞迁移至梗死部位,并分化为心肌细胞、平滑肌细胞、血管内皮细胞,从而减少梗死面积,改善心脏功能,但动物实验结果仍存在着矛盾,临床应用的有效性和安全性还需进一步探讨.     

粒细胞集落刺激因子在急性心肌梗死治疗中的作用

急性心肌梗死（acute myocardial infarction．AMI）发病率、致残率和死亡率高,严重危害健康。由于成人体内心肌细胞缺乏再生能力,心肌梗死的坏死区将由结缔组织替代,梗死周围心肌重新排列重构心肌,并最终发展为心力衰竭。心力衰竭是AMI患者死亡的主要原因,目前治疗药物和介入疗法无法逆转已坏死的心肌细胞。     

粒细胞集落刺激因子动员骨髓干细胞治疗心肌梗死

急性心肌梗死(acute myocardial infarction，AMI)作为冠心病中最危重的临床类型，是造成冠心病患者死亡的主要原因。通常认为心肌细胞为永久型细胞，没有分裂增殖的能力，心肌梗死灶只能由疤痕组织填充。虽然最近研究报道心肌梗死后有很少量心肌细胞发生分裂增殖，但不能完整修复梗死的心肌组织     

粒细胞集落刺激因子治疗心肌梗死

粒细胞集落刺激因子治疗心肌梗死，能动员骨髓干细胞迁移至梗死部位，并分化为心肌细胞、平滑肌细胞、血管内皮细胞，从而减少梗死面积，改善心脏功能，但动物实验结果仍存在着矛盾，临床应用的有效性和安全性还需进一步探讨。     

粒细胞集落刺激因子动员自体外周血干细胞移植治疗急性心肌梗死的临床研究

目的观察经皮经腔冠状动脉内移植自体外周血干细胞(PBSC)治疗急性心肌梗死(AMI)的疗效。方法自2003年11月至2005年1月共入选AMI患者70例,随机分为干细胞移植组和对照组,两组均为35例。干细胞治疗组在常规AMI治疗(药物与介入治疗)基础上应用粒细胞集落刺激因子(GCSF)皮下注射动员自体骨髄干细胞,连用5天,第6天分离外周血干细胞悬液,将采集后的干细胞悬液经OVERTHEWIRE球囊导管中心腔注入梗死相关动脉(IRA),进行外周血干细胞移植;对照组经AMI常规方法(药物与介入)治疗。在外周血干细胞动员、采集及经冠状动脉回输过程中观察其不良反应。两组患者在移植前及移植后6个月应用超声心动图评价左室形态及心功能变化,室壁节段性运动积分;比较两组患者生存率及心脏事件发生率。结果6个月时干细胞移植组心脏收缩末容积(ESV)明显减小[(63.8±23.9)ML比(52.6±20.3)ML,P=0.01],舒张末容积(EDV)无显著性变化[(134.2±36.7)ML比(119.2±30.3)ML,P=0.07];左室射血分数(LVEF)显著增高[(50.0±8.2)%比(57.1±7.8)%,P<0.001];左室壁节段性运动积分指数(WMSI)明显减低[(1.219±0.190)比(1.101±0.118),P<0.001]。对照组介入术前及术后6个月随访ESV、EDV、LVEF及WMSI均无统计学差异(P=0.490、0.259、0.117、0.395)。两组术后6个月生存率及心脏事件发生率无统计学差异。不良反应:在PBSC动员、分离、采集及回输中总的不良反应共25例次,其中动员时不良反应占37.1%(13/35),分离和采集中的不良反应占14.3%(5/35),经冠状动脉回输过程中出现的不良反应占20.0%(7/35)。结论经皮经腔冠状动脉内移植自体PBSC治疗AMI可以在近期有效地减少心肌梗死缺血面积,减轻左室重构,改善心功能。     

粒细胞-巨噬细胞集落刺激因子治疗缺血性脑血管病

粒细胞-巨噬细胞集落刺激因子(granulocytc macrophage-colony stimulating factor,GM-CSF)是一种多功能生长因子,可刺激造血祖细胞(hemopoietic progenitor cell,HPC)增殖、分化和成熟并从骨髓向外周转移,诱导多种细胞增殖和分化.近年来的研究表明,GM-CSF在抗凋亡、诱导神经元分化和血管生成方面发挥着重要的作用,将是缺血性脑血管病治疗的新补充.文章就GM-CSF在缺血性脑血管病治疗中的作用做了综述.     

粒细胞集落刺激因子与葛根素治疗急性脑梗死的临床对照研究

目的比较粒细胞集落刺激因子(G-CSF) 与葛根素对急性脑梗死治疗的有效性和安全性,并分析其不同作用机制.方法 63例急性脑梗死病人随机分为3组,分别给予常规西药(对照组)21例、常规西药加用G-CSF(G-CSF组) 21例和常规西药加葛根素(葛根素组)21例,观察治疗前及治疗后14 d时神经功能缺损程度,并随访3个月时临床神经功能及日常生活活动能力.结果 63例均完成了3个月的观察.治疗后14 d时神经功能缺损评分G-CSF组较对照组疗效比较无统计学意义,而葛根素组较对照组疗效间比较有统计学意义,治疗后3个月时神经功能缺损评分G-CSF组和葛根素组较对照组疗效比较均有统计学意义,而G-CSF组和葛根素组疗效比较亦有统计学意义.G-CSF组和葛根素组未出现严重不良反应.结论 G-CSF及葛根素对治疗急性脑梗死安全有效,治疗机制虽有所不同,但G-CSF显示了更好的远期治疗效果.     

G／GM—CSF体外对骨髓增生异常综合征患者造血祖细胞的作用

对粒细胞集落刺激因子,粒－单细胞集落刺激因子体外在骨髓增生异常综合征患者骨髓造血祖细胞中的作用进行了研究。结果发现ＭＤＳ患者的粒－单系集落形成单位、红系集落形成单位数量明显低于正常人。     

骨髓间充质干细胞治疗缺血性脑损伤的研究进展

骨髓间充质干细胞在体外特定的条件下,可诱导分化成神经细胞,这一生物学特性为缺血性脑损伤的细胞和基因治疗带来了新的希望,为神经系统疾病的治疗和康复展示了美好的前景。文章对其研究现状及进展做了综述。     

A Meta-Analysis of Stem Cell Mobilization by Granulocyte Colony-Stimulating Factor in the Treatment of Acute Myocardial Infarction

Objective This project was aimed at evaluating the safety and efficacy of granulocyte colony-stimulating factor (G-CSF) as an adjunctive therapy to the standard therapy [percutaneous coronary interventions (PCI) and conventional medication] after acute myocardial infarction (AMI). Methods A meta-analysis of randomized controlled trials (RCTs) of G-CSF as an adjunctive therapy to standard therapy versus standard therapy was performed. The endpoints were defined as (1) target-vessel restenosis, (2) cumulative cardiac events (CCEs) that were a combined endpoint of all-cause deaths, reinfarction, and target-vessel revascularization, and (3) the changes in left ventricular ejection fraction (LVEF) from baseline to follow-up. Results 320 patients were involved in 6 RCTs, of whom 160 were randomized to the G-CSF group and 160 to the control group. The follow-up period was 6.17 ± 3.49 months. There was no significant difference in the risk of target-vessel restenosis (P = 0.90) or CCEs (P = 0.59) between the two groups. When a pooled analysis of the changes in LVEF was performed with fixed-model effect, a significant heterogeneity was observed (P < 0.00001). The pooled analysis was thus conducted with random-model effect and did not show a significant improvement as compared to the control group (P = 0.34). A similar result was found in the sensitivity analysis based on five placebo-controlled trials involving 270 patients (P = 0.94). Conclusions G-CSF as an adjunctive therapy to standard therapy for patients with AMI may be safe. However, there is not much supporting evidence that this treatment could further improve LVEF. Since there are relatively few RCTs that meet the inclusion criteria and are heterogeneous in design, further research is required.     

Granulocyte-Macrophage Colony Stimulating Factor: An Adjuvant for Cancer Vaccines

Granulocyte-macrophage colony stimulating factor (GM-CSF) enhances immune responses by inducing the proliferation, maturation, and migration of dendritic cells, and the expansion and differentiation of B and T lymphocytes. There is significant data in pre-clinical animal models demonstrating the adjuvant effects of GM-CSF in a variety of cancer vaccine approaches, including cellular vaccines, viral vaccines, peptide and protein vaccines, and DNA vaccines. GM-CSF is an attractive vaccine adjuvant because of its immune modulation effects and low toxicity profile. The results in animal models have been confirmed in pilot clinical trials and several clinical trials are currently ongoing.     

肌苷对大鼠脑缺血再灌注后神经细胞干细胞因子mRNA表达的影响

目的:研究大鼠缺血再灌注后神经细胞干细胞因子(stemcellfactor,SCF)mRNA表达的变化和肌苷对它的影响。方法:成年健康雌性SD大鼠68只,随机分为缺血再灌注组(n=64)和假手术组(n=4),前者随机分为肌苷处理组(100mg/kg,腹腔注射;n=32)和对照组(n=32),然后各组再随机分为缺血1.5h再灌注2h、6h、12h、24h、2d、3d、7d、14d组(每组4只)。用线栓法制作大脑中动脉缺血再灌注模型。用原位杂交法检测脑组织SCFmRNA表达。结果:对照组缺血侧皮质除2h、6h、12h以外,纹状体除2h、6h以外,室旁区除2h、14d以外,各时间点SCFmRNA均显著高于假手术组(P<0.05)。与对照组相比,肌苷处理组14d时皮质和纹状体SCFmRNA表达有所降低,3d和7d时皮质、纹状体和室旁区SCFmRNA表达均显著增高(P<0.01)。结论:肌苷可增加大鼠脑缺血再灌注后SCFmRNA表达,可能在促进神经干细胞增殖方面起一定作用。     

Granulocyte Macrophage-Colony Stimulating Factor receptor expression on human cardiomyocytes from end-stage heart failure patients

BACKGROUND: In remodelling ventricles, the progression of heart failure is associated with structural changes involving the extra-cellular matrix (ECM) and the cytoskeleton of cardiomyocytes, associated with fibrosis, cellular damage and death. The role of some cytokines and haematopoietic growth factors in the mechanism of both damage and regeneration of cardiac tissue during acute myocardial infarction has been demonstrated. Following heart damage, the development of scarred tissue was considered to be the only outcome, since myocytes were considered to be terminally differentiated cells. However, recent studies in animal models and adult human hearts have shown that myocytes can proliferate under the modulation of several factors. AIMS: To assess Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) receptor expression in healthy and diseased human hearts, and to evaluate the possible role of GM-CSF and its receptor in the regeneration of cardiac tissue in chronic cardiomyopathy. METHODS AND RESULTS: GM-CSFR expression in human cardiac tissue from explanted hearts of ten patients with end-stage heart failure and in cardiac biopsies from eight normal human hearts was studied by immunohistochemistry, and cellular and molecular biology assays. Our results demonstrated an increase in GM-CSFR in cardiomyocytes from end-stage heart failure tissues as compared to normal control tissues. CONCLUSIONS: We hypothesize that GM-CSF plays a role in apoptotic and/or ECM deposition processes as well as in cytoskeleton modification in the myocardium.     

干扰素调节因子-1与缺血性脑损伤

干扰素调节因子-1（1RF-1）参与炎症、细胞周期和细胞凋亡等的分子机制。研究表明，缺血性脑损伤后期1RF-1的表达明显增加，表明其是在基因水平参与缺血性脑损伤正反馈机制的因子，是联系脑缺血早期和晚期损伤的重要因子之一。因此，1RF-1成为在脑缺血治疗中阻断级联反应的靶点之一。     

粒细胞集落刺激因子对急性高原MODS心肌保护作用的研究

目的探讨粒细胞集落刺激因子(G-CSF)对高原急性多脏器功能不全综合征(M ODS)大鼠心肌的保护作用。方法在马汉山梯度(海拔3 900 m)建立20只大鼠M ODS模型,观察组(10只)造模前皮下注射G-CSF 10μg/(kg.d),连用5 d;对照组不用药。造模后24 h处死两组大鼠,取心肌标本,测定心肌梗死面积、左心室收缩及舒张期功能、心肌线粒体三磷酸腺苷(ATP)含量及F as mRNA、caspase-3的表达。结果观察组较对照组心肌收缩及舒张期功能增高明显,心肌ATP含量增加,心肌细胞凋亡数量减少,心肌中F as mRNA、caspase-3表达下降,心肌梗死面积缩小。结论G-CSF可提高高海拔地区M ODS大鼠心功能,其机制可能为动员骨髓基质干细胞修复坏死的心肌组织。