Impaired neutrophil chemotaxis in Crohn's disease relates to reduced production of chemokines and can be augmented by granulocyte-colony stimulating factor

BACKGROUND: Defective neutrophil recruitment has been described as a primary pathogenic abnormality in Crohn's disease. Cantharidin-induced blisters provide a novel investigative tool to assess cellular influx and inflammatory mediator production during acute inflammation and allows the effects of therapy on these parameters to be measured. AIMS: To determine whether reduced neutrophil tissue penetration in Crohn's disease relates to impaired production of inflammatory mediators, and whether it can be reversed by granulocyte-colony stimulating factor (G-CSF). METHODS: Neutrophil and monocyte/macrophage populations and inflammatory mediators were measured in cantharidin blisters at 24 h. Neutrophil chemotaxis was assessed in vitro using blister fluid as the chemoattractant. The effect of s.c. G-CSF on blister phenotype was determined. RESULTS: Significantly fewer neutrophils migrated into blisters in Crohn's patients. The production of neutrophil chemokines, but not other inflammatory mediators, was reduced. This significantly correlated with reduced chemotaxis in vitro. Differences were unrelated to caspase-recruitment domain 15 genotype. G-CSF significantly increased blister neutrophil concentrations in control subjects and Crohn's patients. CONCLUSIONS: Reduced neutrophil migration during acute inflammation in Crohn's disease is associated with impaired production of appropriate chemoattractants. G-CSF therapy increases neutrophil tissue migration, which may partially account for its observed therapeutic effect.     

Partial correction of neutrophil dysfunction by oral galactose therapy in glycogen storage disease type Ib

Glycogen storage disease type Ib (GSD-Ib) is characterized by impaired glucose homeostasis, neutropenia and neutrophil dysfunction.Mass spectrometric glycomic profiling of GSD-Ib neutrophils showed severely truncated N-glycans, lacking galactose. Experiments indicated the hypoglycosylation of the electron transporting subunit of NADPH oxidase, which is crucial for the defense against bacterial infections. In phosphoglucomutase 1 (PGM1) deficiency, an inherited disorder with an enzymatic defect just one metabolic step ahead, hypogalactosylation can be successfully treated by dietary galactose. We hypothesized the same pathomechanism in GSD-Ib and started a therapeutic trial with oral galactose and uridine. The aim was to improve neutrophil dysfunction through the correction of hypoglycosylation in neutrophils. The GSD-Ib patient was treated for 29 weeks. Monitoring included glycomics analysis of the patient's neutrophils and neutrophil function tests including respiratory burst activity, phagocytosis and migration. Although no substantial restoration of neutrophil glycosylation was found, there was partial improvement of respiratory burst activity.     

Capillary electrophoretic separation of poly(ethylene glycol)-modified granulocyte-colony stimulating factor

We evaluated the utility of capillary electrophoretic methods for analyzing poly(ethylene glycol) (PEG)-modified granulocyte-colony stimulating factor (G-CSF), a long-acting form of GCSF for the treatment of cancer therapy-induced neutropenia. Low- and high-molecularweight PEG-G-CSF conjugates prepared with aldehyde-activated PEG-5K and PEG-20K were separated by high-performance size-exclusion chromatography (HP-SEC), capillary zone electrophoresis (CZE), and sodium dodecyl sulfate-capillary gel electrophoresis (SDS-CGE). HPSEC showed low resolution for separating mono- and di-PEG-G-CSFs. SDS-CGE had higher resolution, but required a long analysis and had low peak efficiency. CZE could successfully separate both PEG-5K- and PEG-20K-conjugated G-CSFs with a running time of 20 min and high peak efficiency. In conclusion, CZE was better than SDS-CGE for separating PEG-G-CSF conjugates and will be useful for PEGylation studies, such as reaction monitoring for optimization of the PEGylation reaction, and purity and stability tests of PEG-G-CSF.     

Mobilization of peripheral blood stem cells by granulocyte-colony stimulating factors: comparison of a standard dose of glycosylated and mutated granulocyte-colony stimulating factor in non-Hodgkin's lymphoma patients following CHOP therapy

The effects of granulocyte-colony stimulating factor (G-CSF) have been studied in several clinical settings. G-CSFs are widely used to stimulate the production of granulocytes and are well known to mobilize peripheral blood stem cells (PBSCs). However, very few studies have examined differences among G-CSFs. The aim of this study was to compare the mobilization of PBSCs induced by a standard dose of two G-CSFs following biweekly cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) therapy. Using a standard dose of G-CSF, we conducted a randomized, crossover trial that compared the efficacy of two kinds of G-CSF, glycosylated [lenograstim (2 micrograms/kg)] and mutated [nartograstim (1 microgram/kg)], on PBSC mobilization in 10 patients with non-Hodgkin's lymphoma after biweekly CHOP chemotherapy. Lenograstim (2 micrograms/kg) was more effective in shortening the duration of neutropenia than nartograstim (1 microgram/kg) (3.8 days vs. 5.0 days, p < 0.05, the number of days for the neutrophil count to reach 5 x 10(9)/l from nadir). The number of CD34+ cells and granulocyte-macrophage colony forming units (GM-CFU) was higher for lenograstim but no statistically significant difference between the two groups was found. Glycosylated G-CSF is more effective than mutated G-CSF in shortening the duration of neutropenia. As for the mobilization of CD34+ cells and the number of CFU-GM, there was a tendency to increase in the lenograstim group but no statistically significant differences were found.     

Intranasal absorption of granulocyte-colony stimulating factor (G-CSF) from powder formulations, in sheep.

Granulocyte-colony stimulating factor (G-CSF) was administered to sheep in three different nasal formulations and as a subcutaneous injection. The nasal formulations were: a solution containing L-alpha-lysophosphatidylglycerol (LPG), a powder formulation comprising small starch microspheres (SSMS) and a powder formulation comprising SSMS and LPG. Absorption of G-CSF was assessed directly by quantitation in plasma and indirectly by measurement of the pharmacodynamic response in terms of leucocyte and neutrophil counts. After the nasal delivery of the G-CSF powder formulation containing SSMS and LPG the absorption of G-CSF was significantly higher (P<0.01) than that from the simple nasal solution or the powder without the enhancer, but the resulting pharmacological response was not significantly different. The bioavailability of G-CSF from the powder formulation containing SSMS and LPG relative to the subcutaneous injection was 8.4% (+/-3.4). We also found that at the respective G-CSF doses investigated, the pharmacodynamic response of this nasal formulation, was similar to that obtained after the subcutaneous administration. The study indicates that the powder formulation containing enhancers could offer an alternative delivery route for G-CSF in the form of intranasal administration.     

A potential for granulocyte-colony stimulating factor for use as a prophylactic agent for heatstroke in rats

Heatstroke is a form of excessive hyperthermia associated with a systemic inflammatory response that leads to multi-organ dysfunction in which central nervous system disorders predominate. Herein we determined to ascertain whether heat-induced multi-organ dysfunction in rats could be attenuated by granulocyte-colony stimulating factor (G-CSF) preconditioning. Anesthetized rats were divided into 2 major groups and given vehicle solution (isotonic saline, 0.3 ml, subcutaneously) or G-CSF (50-200 μg/kg body weight in 0.3 ml normal saline, subcutaneously) daily and consecutively for 5 days before the start of thermal experiments. They were exposed to an ambient temperature of 43°C for 68 min to induce heatstroke. G-CSF preconditioning significantly prolonged the survival time in heatstroke rats in a dose-related way (82-98 min vs 127-243 min). The non-preconditioning heatstroke animals showed hyperthermia, arterial hypotension, increased serum levels of systemic inflammatory response molecules, increased hypothalamic apoptotic cell numbers as well as neuronal damage scores, and increased serum levels of renal and hepatic dysfunction indicators. These heatstroke syndromes could be significantly reduced by G-CSF preconditioning. Thus our results revealed a potential for G-CSF used as a prophylactic agent for heatstroke in rats.     

Simultaneous treatment with carbimazole and granulocyte-colony stimulating factor in a patient with thyrotoxicosis and carbimazole induced neutropenia

We describe a patient who was admitted with uncontrolled thyrotoxicosis and carbimazole induced neutropenia. She required 80 mg of carbimazole daily. The patient declined radio-iodine treatment because she had a little child and wished to have thyroid surgery. She received four doses of filgrastim (Granulocyte-colony stimulating factor) which maintained the neutrophil count within a reasonable level while she continued to receive carbimazole to prepare her for surgery. After a curative subtotal thyroidectomy and discontinuation of the carbimazole, the patient’s white cell count remained normal. Subsequently the patient was euthyroid on levothyroxine replacement. Carbimazole should always be discontinued if neutropenia occurs but this case demonstrates that in exceptional circumstances filgrastim can be an effective therapy while continuing carbimazole in the short term.     

Increased granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) levels in BAL fluid from patients with sulfur mustard gas-induced pulmonary fibrosis.

The objective of this article was to show the role of cytokines in the pathogenesis of pulmonary fibrosis due to sulfur mustard gas inhalation. Eighteen veterans with mustard gas-induced pulmonary fibrosis and 18 normal patients were used as controls. Bronchoalveolar larvage (BAL) and analyses of BAL fluids for cellular and cytokine levels were performed. There was a significant difference in granulocyte colony stimulating factor (G-CSF) level in the BAL fluid of patients and the controls (p < 0.0001). Granulocyte-macrophage colony stimulating pulmonary fibrosis (GM-CSF) BAL levels were significantly increased in patients with pulmonary fibrosis (PF) in comparison with controls (p < 0.0001). Patients with PF have highly significant increases in IL-8 level compared to controls (87.94 +/- 59.63 vs. 8.66 +/- 6.97 g/mL(1); p < 0.0001) as well. IL-8 and G-CSF levels in BAL fluid correlate only with the percentage and the absolute number of neutrophils of the BAL fluid in patients with PF (p = 0.02/p = 0.01; p = 0.01/p = 0.01; respectively). A significant correlation was found between GM-CSF BAL fluid level and the percentage and the absolute number of the BAL fluid eosinophils (p = 0.04 and p = 0.03). Neutrophils alveolitis, the presence of eosinophils, and higher concentrations of interleukin-8, G-CSF, and GM-CSF in BAL fluid are associated with the development of fibrosis in sulfur mustard victims.     

重组人粒细胞集落刺激因子诱导急性脑梗死大鼠神经血管再生的研究

目的检测大鼠急性脑梗死后重组粒细胞集落刺激因子(rh G-CSF)对脑内nestin~+及CD34~+细胞表达的影响。方法健康雄性Wistar大鼠随机分为脑梗死组及假手术组、药物组,建立脑梗死模型,流式细胞仪测定凋亡细胞,免疫组织化学法检测梗死区及周边神经上皮干细胞蛋白(nestin)~+、CD34~+细胞的表达。结果药物组凋亡细胞数少于梗死组,梗死区及周边1 d时即出现CD34~+细胞,1周时可检测到nestin~+细胞;假手术组及梗死组梗死区及周边未检测到nestin~+及CD34~+细胞。结论 rh G-CSF可能动员内源性干细胞向神经前体细胞及新生血管分化,并可以减少细胞凋亡。     

Irreversible aggregation of recombinant bovine granulocyte-colony stimulating factor (bG-CSF) and implications for predicting protein shelf life

The kinetics of irreversible aggregation of bovine Granulocyte-Colony Stimulating Factor (bG-CSF) in solution were investigated as a function of temperature (T), concentration, and pH, and analyzed in terms of an Extended Lumry-Eyring model of protein aggregation proceeding via a non-native conformational state. In the spirit of classic Lumry-Eyring models, the observed kinetics are separated into contributions from thermodynamic or conformational stability of unaggregated native and non-native states, and the intrinsic aggregation kinetics of non-native molecules. It is found that a detailed treatment of the intrinsic kinetics coupled with a two-state approximation of the reversible unfolding transition is sufficient to allow quantitative prediction of low-T stability from high-T data despite highly non-Arrhenius kinetics. Accounting for shifts in conformational equilibrium quantitatively captures the non-Arrhenius T dependence, without requiring the assumption of a change in the rate-determining step with T. From a more general perspective, the observed aggregation behavior of bG-CSF is consistent with the rate-determining step being aggregation at T below a crossover temperature T(x) that is inversely related to initial protein concentration. Above T(x), irreversible unfolding is presumably the rate-determining step. The results illustrate that protein aggregation kinetics can, in principle, be predicted quantitatively from so-called accelerated data provided the thermodynamic and kinetic components can be separately extrapolated to longer term storage conditions.     

The intravenous administration of tumor necrosis factor alpha,interleukin 8 and macrophage-derived neutrophil chemotactic factor inhibits neutrophil migration by stimulating nitric oxide production

1. The i.v. administration of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8) and the recently described macrophage-derived neutrophil chemotactic factor (MNCF) inhibits the recruitment of neutrophils to the inflammatory site.
2. Pretreatment of mice with the NO synthase antagonist, N^G-monomethyl-L-arginine (L-NMMA, 15–60 mg kg⁻¹), but not the inactive enantiomer D-NMMA (30 mg kg⁻¹), prevented in a dose-dependent manner the TNF-α, IL-8 and MNCF-mediated inhibition of neutrophil migration into thioglycollate-challenged peritoneal cavities.
3. Treatment of the neutrophils with TNFα (10⁻⁷ M), IL-8 (10⁻⁷ M) or MNCF blocked their migration towards FMLP in the chemotaxis assay. The pretreatment of the neutrophils with L-NMMA (50–200 μM) prevented in a dose-dependent manner the inhibition of FMLP-induced chemotaxis by IL-8, but did not alter the inhibition caused by TNF-α or MNCF. Different concentrations of the NO donors, S-nitroso-N-acetylpenicillamine (SNAP) or 3-morpholino-sydnonimine (SIN-1), did not alter this chemotaxis.
4. Preincubating the neutrophils with L-NMMA (200 μM) significantly increased the TNF-α (10⁻⁷ M) and MNCF-mediated neutrophil adhesion to unstimulated endothelial cells, but had no effect on IL-8 (10⁻⁷ M)-mediated adhesion.
5. Although NO donors did not directly affect the mechanisms of neutrophil motility, NO is involved in the in vitro inhibitory action of IL-8 on chemotaxis. The TNF-α and MNCF-mediated inhibition of neutrophil migration seems to be indirect, by affecting the mechanisms of adhesion. It was concluded that TNF-α-, IL-8- and MNCF-mediated inhibition of neutrophil migration is associated with the stimulation of NO production.

     

Studying the formation of aggregates in recombinant human granulocyte-colony stimulating factor (rHuG-CSF), lenograstim, using size-exclusion chromatography and SDS-PAGE

The stability of proteins is a subject of intense current interest. Aggregation, as a dominant degradation pathway for therapeutic proteins, may cause multiple adverse effects, including loss of efficacy and immunogenicity. In the present study, the formation of aggregates in lenograstim under physiological conditions was monitored. For this purpose, a simple and selective size-exclusion high-performance liquid chromatography method for detection and separation of aggregates from intact protein was developed. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis was performed under reducing and non-reducing conditions to determine the nature of aggregate bond formation. Using both techniques, the presence of a low aggregate content attached via disulfide bonds was detected.     

Tissue factor contributes to neutrophil CD11b expression in alpha-naphthylisothiocyanate-treated mice

Cholestatic liver injury induced by alpha-naphthylisothiocyanate (ANIT) is provoked by injury to intrahepatic bile ducts and the progression of hepatic necrosis requires the procoagulant protein tissue factor (TF) and extrahepatic cells including neutrophils. Recent studies have shown that myeloid cell TF contributes to neutrophil activation. We tested the hypothesis that myeloid cell TF contributes to neutrophil activation in ANIT-treated mice. TF activity in liver homogenates increased significantly in TF^flox/flox mice treated with ANIT, but not in TF^flox/flox/LysMCre mice (TF^ΔMyeloid mice), which have reduced TF expression in monocytes/macrophages and neutrophils. Myeloid cell-specific TF deficiency did not alter expression of the chemokines KC or MIP-2 but reduced hepatic neutrophil accumulation in ANIT-treated mice at 48 h as indicated by tissue myeloperoxidase (MPO) activity. Myeloid cell TF deficiency significantly reduced CD11b expression by blood neutrophils in ANIT-treated mice, and this was associated with reduced plasma MPO protein levels, an index of neutrophil degranulation. However, myeloid cell-specific TF deficiency had no effect on ANIT-induced coagulation cascade activation. The increase in serum ALT and ALP activities in ANIT-treated mice was reduced by myeloid cell TF deficiency (p < 0.05), but the myeloid cell TF deficiency did not reduce hepatic necrosis at 48 h, as determined by histopathology and morphometry. The results suggest that myeloid cell TF contributes to neutrophil CD11b expression during cholestasis by a coagulation-independent pathway. However, the resultant reduction in neutrophil accumulation/activation is insufficient to substantially reduce ANIT hepatotoxicity, suggesting that myeloid cell TF is only one of many factors modulating hepatic necrosis during cholestasis.     

长效粒细胞集落刺激因子用于预防化疗后感染的临床研究设计考虑

化疗是治疗恶性肿瘤的一种重要方法，但化疗可引起多种不良反应，其中包括中性粒细胞减少并继发感染。本文简要介绍长效粒细胞集落刺激因子预防化疗后感染临床研究设计的考虑要点，旨在为此类新药的研发提供参考。     

Treatment with granulocyte-colony stimulating factor in patients with acute myocardial infarction. Evidence for a stimulation of neovascularization and improvement of myocardial perfusion

BACKGROUND: Stem cell therapy has been suggested to be beneficial in patients after acute myocardial infarction (AMI). Strategies of treatment are either a local application of mononuclear bone marrow cells (BMCs) into the infarct-related artery or a systemic therapy with the granulocyte-stimulating factor (G-CSF) to mobilize BMCs. Nevertheless, the mechanisms responsible for improvement of cardiac function and perfusion are speculative at present. This study has been performed to investigate the effect of G-CSF on systemic levels of vascular growth factors and chemokines responsible for neovascularization, that might help to understand the positive effects of a G-CSF therapy after AMI. METHODS AND RESULTS: Five patients in the treatment group and 5 patients in the control group were enrolled in this study. The patients in the treatment group received 10 microg/kg bodyweight/day of G-CSF subcutaneously for a mean treatment duration of 6.6 +/- 1.1 days. In both groups, levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and monocyte chemotactic protein-1 (MCP-1) were measured on day 2 to 3 and day 5 after AMI. The regional wall perfusion and the ejection fraction (EF) were evaluated before discharge and after 3 months with ECG-gated MIBI-SPECT and radionuclide ventriculography, respectively. Significant higher levels of VEGF (p < 0.01), bFGF (p < 0.05) and MCP-1 (p < 0.05) were found in the treatment group compared to the control group. Levels of VEGF and bFGF remained on a plateau during the G-CSF treatment and decreased significantly in the control group. The wall perfusion improved significantly within the treatment group and between the groups (p < 0.05), respectively. The EF improved significantly within the treatment group (p < 0.05), but the change of the EF between the groups was not significant. CONCLUSION: In patients with AMI, the treatment with G-CSF modulates the formation of vascular growth factors that might improve neovascularization and result in an improved myocardial perfusion and function.     

Inhibition of inducible nitric oxide synthase gene expression and nitric oxide synthesis in vascular smooth muscle cells by granulocyte-colony stimulating factor in vitro.

Clinical and experimental evidence suggests that granulocyte-colony stimulating factor (G-CSF) acts as an anti-inflammatory modulator with beneficial effects in severe inflammatory diseases, e.g., sepsis and septic shock. Excessive production of nitric oxide (NO) is regarded as a potent mediator of the vascular changes leading to systemic hypotension that occurs during sepsis. Therefore, the aim of the present study was to investigate the influence of G-CSF on inducible nitric oxide synthase (iNOS) gene expression and NO synthesis in vascular smooth muscle cells (VSMC). Qualitative and quantitative analyses of iNOS cDNA revealed that G-CSF significantly reduced interferon-gamma/lipopolysaccharide (IFN-gamma/LPS) dependent iNOS gene expression (P < 0.05) following 6, 18, 24, and 48 h incubation periods. In addition, the co-application of G-CSF resulted in a decreased IFN-gamma/LPS mediated iNOS protein generation as detected by immunoblotting methods after 24 and 48 h. Measurement of the stable NO metabolites showed a significant reduction of nitrite/nitrate concentrations following co-incubation of VSMC with G-CSF + IFN-gamma/LPS (242.57 +/- 10.73 nmol NO2-/NO3-/mg cell protein, n = 8) as compared to IFN-gamma/LPS treatment (306.20 +/- 19.26 nmol NO2-/NO3-/mg cell protein, n = 8, P < 0.05) following a 24-h incubation protocol. This inhibitory effect of G-CSF was still present after a 48 h incubation period (G-CSF + IFN-gamma/LPS: 319.56 +/- 6.26 nmol NO2-/NO3-/mg cell protein; IFN-gamma/LPS: 489.20 +/- 27.15 nmol NO2-/NO3-/mg cell protein (P < 0.05), n = 8, respectively). The present findings suggest that inhibition of iNOS gene expression and NO generation in VSMC might be one of the protective anti-inflammatory effects of G-CSF during sepsis.     

Improvement of an impaired chemiluminescence response to formyl-methionyl-leucyl-phenylalanine in neutrophils from patients with non insulin dependent diabetes mellitus by recombinant human granulocyte-colony stimulating factor

To explore the possibility that b type recombinant human granulocyte-colony stimulating factor (rhG-CSF) is a useful drug to prevent the morbidity and mortality caused by infections in diabetic patients, we have studied effects of rhG-CSF on chemiluminescence amplified by a luciferin analog (CLA-DCL) and luminol (L-DCL) in response to formyl-Methionyl-Leucyl-Phenylalanine (fMLP) in neutrophils from patients with non insulin dependent diabetes mellitus (NIDDM) (diabetic neutrophils) and healthy subjects (control neutrophils). Both CLA-DCL and L-DCL in diabetic neutrophils were significantly reduced, and L-DCL was more sensitive to this suppression than CLA-DCL. RhG-CSF did not change the basal chemiluminescence in control and diabetic neutrophils, but it primed CLA-DCL and L-DCL. Although, in diabetic neutrophils, the priming effect of rhG-GSF on both CLA-DCL and L-DCL was less compared to that in control neutrophils, L-DCL was more sensitive to this priming effect than CLA-DCL. Because bacterial infection is still an important cause of the morbidity and mortality in diabetic patients, these data suggest that rhG-CSF is a useful drug to prevent the aggravation of bacterial infection in patients with NIDDM.     

围术期应用粒细胞集落刺激因子对大鼠心脏术后心功能的影响

目的 探讨围术期应用粒细胞集落刺激因子(G-CSF)对大鼠心脏术后心功能的影响.方法 将Wistar雄性大鼠随机分为3组,每组10只,暴露心脏后于左心室沿冠状动脉左前降支附近作一切口后立即缝合切口并关胸.对照组不使用G-CSF,仅完成手术过程;G-CSF预处理组术前通过鼠尾静脉注射G-CSF 5 d；G-CSF预处理+心内注射组除术前通过鼠尾静脉注射G-CSF 5 d外,手术过程中将G-CSF直接注射在心室切口周围.术后第7、28天行超声心动图检查评价心脏结构和心功能.结果 第7大时,对照组左心室射血分数(LVEF)和缩短分数(FS)分别为(52.8±2.9)％、(22.2±1.4)％,G-CSF预处理组和G-CSF预处理+心内注射组LVEF[分别为(56.5±4.3)％、(61.2±3.6)％]、FS[分别为(25.2±2.5)％、(29.5±2.3)％]均明显高于对照组,差异有统计学意义(均P＜0.05);G-CSF预处理组和G-CSF预处理+心内注射组左心室收缩末内径(LVESD)[分别为(6.25±0.92)、(5.51±0.85)mm]和左心室收缩末容量(LVESV)[分别为(0.57±0.18)、(0.44±0.14)ml]低于对照组[分别为(6.60±1.10)mm、(0.67±0.31)ml],G-CSF预处理+心内注射组LVESD和LVESV低于G-CSF预处理组,差异均有统计学意义(均P＜0.05).第28大时G-CSF预处理组和G-CSF预处理+心内注射组的LVEF[分别为(59.6±4.7)％、(63.8±1.9)％]和FS[分别为(26.2±2.8)％、(30.9±1.6)％]均明显高于对照组[分别为(53.4±3.6)％、(23.6±1.7)％],LV ESD[分别为(5.92±0.72)、(5.35±0.54)mm]、左心室舒张末内径(LVEDD)[分别为(7.48±0.61)、(7.26 ±0.55)mm] 、LVESV [分别为(0.49±0.14)、(0.41±0.08)m1]、左心室舒张末容量(LVEDV)[分别为(1.05±0.25)、(1.02±0.27)ml]低于对照组[分别为(6.98±0.37)mm、(8.04±0.42)mm、(0.76±0.15)ml、(1.37±0.18)ml],差异均有统计学意义(均P＜0.05);G-CSF预处理+心内注射组LVEF、FS明显高于G-CSF预处理组,LVESD、LVEDD、LVESV、LVEDV明显低于G-CSF预处理组,差异均有统计学意义(均P＜0.05).结论 围术期应用G-CSF可明显改善大鼠心脏术后心脏收缩及舒张功能.