【摘要】 目的:考察SeV18+hFGF2/dF(碱性成纤维细胞生长因子仙台病毒载体)的安全性。方法:本研究采用W istar大鼠,120只,雌性各半,随机分为4组分别给予剂量为1×108、4×108及4×109C IU.kg-1的SeV18+hFGF2/dF和磷酸盐缓冲液。肌肉注射给药,每天给药1次,连续给药14天,停药后继续观察4周。本报告总结了给药后对大鼠生理、生化、脏器病理指标的影响,检测了给药后动物抗体的产生情况。结果:反复给药后对动物的生理观察指标未见影响;对动物的血清生化指标无明显影响;血液学指标检测可见红细胞计数(RBC)、血红蛋白含量(HGB)、红细胞压积(HCT)降低,淋巴细胞百分数(L)增高,网织红细胞计数(Ret)增高等;胸腺和脾脏的脏器重量和脏器系数增大,但各脏器组织结构未见与给药相关的异常改变。反复给药后动物可产生抗体,抗体可中和病毒的活性。结论:大鼠对SeV18+hFGF2/dF肌肉注射给药耐受性良好。更多还原

【Abstract】 Objective: Safety of SeV18~+hFGF2/dF(basic fibroblast growth factor Sendai virus vector) was evaluated.Methods: Wistar rats(n = 120,m:f = 1:1) were randomly assigned to 4 groups,dosing with SeV18+hFGF2/dF of 1×10~8,4×10~8,4×10~9 CIU.kg-1, and PBS buffer,respectively.Injection was performed intramuscular once everyday for 14 days.Recovery observation was continued until 4 weeks after the end of dosing.Effects on the physiological and clinical chemitry and histology were tested,and the antibody was detected.Results: No effect on physiological parameters was observed after repeated dosing.No significant effect on serum chemical parameters was shown.For hematological parameters,decrease of RBC count,hemoglobin and hematocrit,and increase of count of lymphocytes and reticular RBC were noticed.Weight and organ relative weight of thymus and spleen increased.No abnormal change in the histology of organs related to the administered agent was identified.Antibody could be induced after repeated dosing,which was able to neutralize the activity of virus.Conclusion: Repeated intramuscular injection of SeV18~+hFGF2/dF was well tolerated in rats.更多还原