急性冠状动脉综合征患者血浆氧化型低密度脂蛋白、高敏C反应蛋白与血管内皮损伤的关系

目的观察急性冠状动脉综合征患者外周血浆氧化型低密度脂蛋白、高敏C反应蛋白、循环内皮细胞计数和一氧化氮的变化,探讨氧化型低密度脂蛋白与高敏C反应蛋白的相关性,以及两者与血管内皮损伤的关系,研究其在急性冠状动脉综合征发生和发展中的意义。方法急性冠状动脉综合征患者51例,临床及选择性冠状动脉造影排除冠心病20例为对照组。测定外周血浆中的氧化型低密度脂蛋白、高敏C反应蛋白、循环内皮细胞计数和一氧化氮水平。结果急性冠状动脉综合征组氧化型低密度脂蛋白、高敏C反应蛋白、循环内皮细胞计数较对照组明显升高,分别为氧化型低密度脂蛋白(686±168μg/L比349±172μg/L,P<0.01)、高敏C反应蛋白(6.15±1.75mg/L比1.53±1.64mg/L,P<0.01)、循环内皮细胞计数[(8.9±1.6)×106个/L比(2.4±0.4)×106个/L,P<0.01]。急性冠状动脉综合征组一氧化氮水平较对照组明显降低(52.2±16.5μmol/L比77.3±21.0μmol/L,P<0.05)。血浆氧化型低密度脂蛋白与循环内皮细胞计数(r=0.781,P<0.001)和一氧化氮(r=0.792,P<0.001)均呈正相关,血浆高敏C反应蛋白与循环内皮细胞计数(r=0.776,P<0.001)和一氧化氮(r=0.897,P<0.001)也均呈正相关,血浆氧化型低密度脂蛋白与高敏C反应蛋白呈正相关(r=0.768,P<0.001),血浆循环内皮细胞计数与一氧化氮呈正相关(r=0.951,P<0.001)。结论血浆氧化型低密度脂蛋白、高敏C反应蛋白可能与血管内皮损伤有关,相互协同作用参与了急性冠状动脉综合征的发病过程。

Chronic Toxicity of a Novel Recombinant Human Granulocyte Colony-stimulating Factor in Rats

Objective To assess the severity and reversibility of the chronic toxicity of a novel recombinant human granulocyte colony-stimulating factor (rhG-CSFa) in rats and the dose-effect relationship.Methods A total of 100 Sprague-Dawley rats (equal numbers of male and female) were randomly divided into five groups (20 rats in each group):four groups were treated with rhG-CSFa at 500,100,10,1 μg/kg,respectively,and one group was treated with vehicle only to serve as the control.The rats were received subcutaneous injections of rhG-CSFa or vehicle daily for 13 weeks.During the course of the chronic toxicity study,the physical status,body weight,and food consumption were monitored.Half of the rats in each group (n=10) were sacrificed after the last rhG-CSFa administration,and the other half were sacrificed at five weeks after the last rhG-CSFa administration.Urinalyses,blood biochemistry,hematological analysis,histopathological examination,and immunological tests were performed for each of the rats.Results The hematological analyses revealed that the mean white blood cells count,neutrophils count,and neutrophils percentage were increased in male rats at the dose of 10 μg/kg or higher,and these were related with the biological activity of rhG-CSFa.Some small abnormalities were observed in the spleen of a few rats when used highest dose (500 μg/kg,a dosage of 200 folds higher than the normal clinical dosage),but these abnormalities were recovered within 5-week recovery period.No other rhG-CSFa-related abnormalities were observed in this chronic toxicity study.Conclusion No significant toxicity and immunogenicity are observed with rhG-CSFa administration to rats in the chronic toxicity studies.

Effects of lipopolysaccharide on actin reorganization and actin pools in endothelial cells

Objective: To investigate the dose and time-dep endent effects of lipopolysaccharide (LPS) on cytoskeletal F-acitn and G-actin reorganizations by visualizing their distribution and measuring their contents in human umbilical vein endothelial cell line ECV-304. Methods: F-actin was labeled with rhodamine-phalloidin and G -actin with deoxyribonuclease I (DNase I)conjugated with fluorescein isothiocya nate (FITC). Contents of cytoskeletal proteins were obtained by flow cytometry. Results: F-actin was mainly distributed peripherally in endoth elial cells under normal conditions. LPS stimulation caused the formation of str ess fibers and filopodia. G-actin was normally seen in perinuclear and nuclear areas in control ECV-304 cells. Under LPS stimulation,G-actin dots appeared i n the cytoplasmic region. The actin disorganization was accompanied by the time - and dose- dependent decrease in F-actin pool and increase in G-actin pool . Conclusions: LPS can induce characteristic morphological altera tions of actin cytoskeleton and formation of intercellular gap in endothelial ce lls,accompanied by changes in F-actin and G-actin pools.