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治疗粒细胞缺乏症疗效观察

1999～2003年，我院应用重组粒细胞集落刺激因子(rhG-CSF)治疗粒细胞缺乏症，疗效较好。现报告如下。     

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

急性心肌梗死是冠心病的一种严重类型，能够导致心肌细胞数量减少和心肌组织瘢痕形成，使心功能受损，发生心力衰竭，是目前心力衰竭的主要原因。近年来，许多研究发现粒细胞集落刺激因子（granulocyte—colony stimulating factor，G-CSF）具有促进心肌梗死后的组织修复和改善心功能的作用，为急性心肌梗死的治疗提供了又一新途径。国内外的动物实验和临床研究发现G-CSF可能通过多种机制影响心功能，现将其相关机制的研究综述如下。     

粒细胞集落刺激因子治疗急性心肌梗死

目前,急性心肌梗死（AMI）患者即使接受及时的再灌注治疗,仍有较高的死亡率[1]。AMI发生后心肌细胞数量减少,只有极少量的心肌细胞发生分裂增生,但不能完整修复心肌组织,25%的患者将出现继发于心肌梗死的心室重构、     

粒细胞集落刺激因子动员骨髓干细胞治疗急性心肌梗死的观察

目的探讨粒细胞集落刺激因子(G-CSF)动员的骨髓来源干细胞对急性心肌梗死(AMI)的治疗作用.方法 27例AMI病人随机分为治疗组和对照组,治疗组连续3 d给予G-CSF 300 μg/d,用201Tl心肌显像比较两组第6天和第30天的梗死面积变化,超声心动图观察3 d内和3个月的心功能变化.结果治疗组第30天的核素梗死缺损区面积明显减少(P＜0.01),核素放射性计数百分比明显增加(P＜0.05),治疗组治疗后各项心功能指标均明显改善(P＜0.01).对照组无明显改变(P＞0.05).结论用G-CSF动员骨髓干细胞可再生成心肌组织,明显缩小AMI的梗死面积及改善心功能.     

粒细胞集落刺激因子动员大鼠骨髓间充质干细胞移植治疗心肌梗死的实验研究

目的 运用粒细胞集落刺激因子诱导骨髓间充质干细胞（MSC）移植归巢到急性心梗区域，研究不同环境下MSC在心肌内的分化状态及程度。方法 选用SD雄性大鼠，体重200～250g，随机分为4组：急性心肌梗死（AMI）干绷胞移植＋粒细胞集落刺激因子（G—CSF）动员组（20只）、AMI干细胞移植组（20只）以及单纯G-CSF组（20只）以及单纯对照组（10只）。于治疗4w后取材，检测心肌梗死区及其周围的血管密度值。免疫组化染色检测抗体增殖细胞核抗原（PCNA）、肌浆蛋白（myogenin）、肌球蛋白（myosin）、缝管连接蛋白43（Cx43）及结蛋白（desinmim）在移植骨髓间充质干细胞中的表达。并用共聚焦免疫荧光双标染色方法标测PCNA、myogenin。结果 胶体金标记的MSC经G-CSF诱导移植到心脏内在梗死部位与心肌生长为一体，颜色为黑色，存HE切片中移植细胞的胞浆呈现紫红色，极易识别。血管密度检测结果显示G-CSF＋MSC移植组心肌梗死区血管密度明显高于其他各组。免疫组化染色检测抗体PCNA、myogenin、myosin、Cx43及desinmim在G-CSF＋MSC移植组心肌梗死区中的表达明显。其他各组未见明显表达。结论 G-CSF能够明显动员MSC归巢，促进梗死区血管新生，在梗死区分化成新的心肌。     

粒细胞集落刺激因子治疗急性心肌梗死的实验研究

目的探讨注射人重组粒细胞集落刺激因子(granulocytecolony-stimulatingfactorG-CSF)动员自体骨髓干细胞对实验急性心肌梗死作用。方法健康杂种猪6头,结扎左冠状动脉前降支距终末端1/3稍高处制成心肌梗死模型,随机分为治疗组及对照组。治疗组注射G-CSF,对照组注射等容积的生理氯化钠溶液。于术前、术后1日、2日、术后1周及术后4周分别测肌酸激酶及其同工酶。术前、术后1周及术后4周分别测左心室射血分数及心肌梗死面积。4周后取出心脏,作病理检查,测定心肌毛细血管密度及对心肌增殖细胞计数。结果治疗组心肌梗死面积缩小,左心室射血分数提高,和对照组比较有统计学意义(P<0.05);治疗组每视野梗死区血管数为(6.2±2.2)根,而对照组为(2.7±1.8)根,差异有统计学意义(P<0.01);治疗组梗死区每视野增殖细胞(Ki-67阳性)数为(5.1±1.4)个,而对照组为(2.4±1.3)个,差异有统计学意义(P<0.01);术后第1天猪心肌肌酸激酶及其同工酶达到高峰,以后逐渐下降,在术后4周基本下降到正常水平。治疗组和对照组差异无统计学意义(P>0.05)。结论注射G-CSF可缩小心肌梗死面积,改善心射血功能,促进心肌梗死处血管再生及细胞增殖,对心肌酶学无明显影响。     

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.     

PPARγ配体对急性心肌梗死心室重构炎症因子的影响

现在对当前急性心肌梗死后心室重构的发病机理认识基础之上,综述了PPARγ的配体在心室重构的发生过程中,对炎症反应的影响的研究进展.     

Treatment of dyskeratosis congenita with Granulocyte Colony-Stimulating Factor and Erythropoietin

Aplastic anaemia is both frequent and difficult to manage in patients with dyskeratosis congenita (DC). We recently treated a 23-year-old male for a year with granulocyte colony-stimulating factor (G-CSF) and erythropoietin (Ep), with an excellent neutrophil response, and a transient effect on haemoglobin levels. G-CSF alone or combined with other cytokines may provide at least a partial effect in pancytopenic patients with DC.     

T-Cell Mineralocorticoid Receptor Deficiency Attenuates Pathologic Ventricular Remodelling After Myocardial Infarction

BackgroundMineralocorticoid receptor (MR) antagonists have been widely used to treat heart failure (HF). Studies have shown that MR in T cells plays important roles in hypertension and myocardial hypertrophy. However, the function of T-cell MR in myocardial infarction (MI) has not been elucidated.MethodsIn this study, we used T-cell MR knockout (TMRKO) mouse to investigate the effects of T-cell MR deficiency on MI and to explore the underlying mechanisms. Echocardiography and tissue staining were used to assess cardiac function, fibrosis, and myocardial apoptosis after MI. Flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect immune cell infiltration and inflammation.ResultsT-cell MR deficiency significantly improved cardiac function, promoted myocardial repair, and inhibited myocardial apoptosis, fibrosis, and inflammation after MI. Luminex assays revealed that TMRKO mice had significantly lower levels of interferon-gamma (IFN-γ) and interleukin-6 (IL-6) in serum and infarcted myocardium than littermate control mice. In cultured splenic T cells, MR deficiency suppressed IL-6 expression, whereas MR overexpression enhanced IL-6 expression. Chromatin immunoprecipitation (ChIP) assay demonstrated that MR bound to the MR response element on the promoter of IL-6 gene. Finally, T-cell MR deficiency significantly suppressed accumulation of macrophages in infarcted myocardium and differentiation of proinflammatory macrophages, thereby alleviating the consequences of MI.ConclusionsT-cell MR deficiency improved pathologic ventricular remodelling after MI, likely through inhibition of accumulation and differentiation of proinflammatory macrophages. At the molecular level, MR may work through IFN-γ and IL-6 in T cells to exert functions in MI.     

Stable Response after Administration of Stem Cell Factor Combined with Granulocyte Colony-Stimulating Factor in Aplastic Anemia

We report successful treatment with 25 microg/kg of recombinant methionyl human stem cell factor (SCF) combined with 400 microg/m2 of recombinant human granulocyte colony-stimulating factor (G-CSF) in 2 patients with aplastic anemia refractory to immunosuppressive therapy. In one patient, hemoglobin levels increased from 6.4 g/dL to 11.3 g/dL after 36 weeks of SCF/G-CSF treatment. Thereafter, the platelet count (24.0 x 10(9)/L) began to improve without the therapy, and as of week 272, the platelet count was 125.0 x 10(9)/L with a leukocyte count of 8.4 x 10(9)/L and a hemoglobin level of 12.9 g/dL. In the other patient, more than 3 years of SCF/G-CSF treatment ameliorated hemoglobin levels and platelet counts from 5.8 g/dL to 15.9 g/dL and 8.0 x 10(9)/L to 50.0 x 10(9)/L, respectively. After cessation of SCF/G-CSF treatment, the positive response was sustained, and the platelet count improved further to 71.0 x 10(9)/L as of week 242. These observations suggest the clinical benefit of SCF/G-CSF administration to patients with refractory aplastic anemia.     

Macrophage-Specific IκB Kinase α Contributes to Ventricular Remodelling and Dysfunction After Myocardial Infarction

Background

The IκB kinase (IKK) complex has been found to have critical functions in cancer and the immune system. In particular, IKKα, which is a member of the IKK complex, has been shown to influence the inflammatory response and malignant diseases. However, the role of IKKα in macrophages after myocardial infarction (MI) remains largely unknown.

Left Ventricular Mural Thrombus after Acute Myocardial Infarction

Left ventricular mural thrombus is a well-recognized complication of acute myocardial infarction. In survivors of infarction, the incidence with which mural thrombus occurs is influenced by the location and magnitude of infarction, so that it occurs commonly in those with large anterior Q-wave infarctions, particularly in the presence of a left ventricular aneurysm. Echocardiography, radionuclide imaging with indium-111 labeled platelets, computerized tomography, and magnetic resonance imaging may be used to identify a left ventricular mural thrombus. Acute and chronic anticoagulation with heparin and warfarin, respectively, is given to prevent further thrombus formation and to reduce the incidence of systemic embolization.     

Granulocyte-colony Stimulating Factor Treatment of Chronic Myocardial Infarction

Purpose  

The aim of this study was to investigate the impact of granulocyte-colony stimulating factor (G-CSF) administration on cardiac function of rats with chronic myocardial infarction through two different protocols: high dose short term and low dose long term protocols.     

Mobilization of Mesenchymal Stem Cells by Granulocyte Colony-stimulating Factor in Rats with Acute Myocardial Infarction

PURPOSE: Intravenous delivery of mesenchymal stem cells (MSCs), a noninvasive strategy for myocardial repair after acute myocardial infarction (MI), is limited by the low percentage of MSCs migration to the heart. The purpose of this study was to test whether granulocyte colony-stimulating factor (G-CSF) would enhance the colonization of intravenously infused MSCs in damaged heart in a rat model of acute MI. METHODS: After induction of anterior MI, Sprague-Dawley rats were randomized to receive: (1) saline (n = 9); (2) MSCs (n = 15); and (3) MSCs plus G-CSF (50 mug/kg/day for 5 consecutive days, n = 13). RESULTS: Flow cytometry revealed that G-CSF slightly increased surface CXCR4 expression on MSCs in vitro. After completion of G-CSF administration, MSCs showed a significantly lower colonization in bone marrow and a trend toward higher localization in the infarcted myocardium. At 3 months, vessel density in the infarct region of heart was significantly increased in MSCs group and trended to increase in MSCs + G-CSF group. However, echocardiographic and hemodynamic parameters, including left ventricular (LV) end-diastolic diameters, ejection fraction, and +/-dP/dt (max), were not statistically different. Morphological analysis showed that infarct size and collagen content were similar in the three groups. Immunohistochemistry revealed that the combined therapy accelerated endothelial recovery of the blood vessels in the ischemic myocardium. However, myocardial regeneration resulting from MSCs differentiation was not observed. CONCLUSIONS: G-CSF enhanced the migration of systemically delivered MSCs from bone marrow to infarcted heart. However, the beneficial effect of this kind of migration is limited, as cardiac function did not improve.