聚乙二醇单修饰重组人粒细胞集落刺激因子对大鼠血液学及骨髓毒性的研究

目的：研究聚乙二醇单修饰重组人粒细胞集落刺激因子（PEG-rhG-CSF）对SD大鼠血液学和骨髓造血的影响，为其应用于临床治疗提供资料。方法：将SD大鼠随机分为3个实验组和1个对照组，分别sc不同剂量PEG-rhG-CSF和溶媒对照品，每周给药3次，连续给药3个月，恢复期2周。在给药和恢复期结束时进行血液学和骨髓检查，并做t-检验统计分析。结果：给药结束后，高中低剂量组血液白细胞计数显著升高（升高了7.8～28.2倍），中性粒细胞计数明显增加（增加了2.5～3.9倍），网织红细胞计数显著增加，淋巴细胞、嗜酸性粒和红细胞计数显著降低；同时，高剂量组血红蛋白量和血小板计数显著降低，高、中剂量红细胞比容显著增加；此外，高中低剂量骨髓红细胞系比例、中幼及晚幼红细胞比例显著降低，而成熟粒细胞比例显著升高（升高了29.1％～79.1％），粒／红（M／E）比值也显著升高（最高增加1.3倍）。上述改变在停药2周后，均恢复到正常水平，与对照组比较均无显著性差异。结论：PEG-rhG-CSF具有明显的促进造血功能，临床可用于治疗肿瘤化疗引起的中性粒细胞减少症。

Study of pegylated recombinant human granulocyte colony-stimulating factor on hematology and marrow toxicity in rats

Objective: To study the impact of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) on hematology and marrow hemopoiesis in SD rat, and to provide an experimental basis for clinical trials. Methods: All rats were randomly divided into three experimental groups and one control group, then respectively administrated with different doses of PEG-rhG-CSF or vehicle control by sc injection once weekly for three months. After administration, two-week recovery period for all groups were followed. The examinations of hematological parameters and marrow were performed at the end of administration and recovery. The results were analyzed by t-test. Results: Compared with the vehicle control group, the leukocyte count (elevated 7.8--28.2 times), neutrophils count (elevated 2.5--3.9 times), and reticulocyte count were significantly increased in the high, middle, and low doses of groups at the end of administration,. In addition, the proportions of erythrocytes series, polychromatic erythroblast, and orthochromatic erythroblast in marrow were significantly decreased while the proportions of mature myeloid cell significantly increased (elevated 29.1%--79.1%). The ratios of myeloid series and erythrocytes series in marrow were also significantly elevated in all groups treated with PEG-rhG-CSF. These changes were restored to normal level after two-week recovery period. Conclusion: Our study suggest that PEG-rhG-CSF has a significant promotion on hemopoiesis function and can be applied for the clinical treatment of granulocytopenia induced by chemotherapy.