人酸性成纤维细胞生长因子与穿膜肽融合蛋白在鼠体内的药代动力学及血脑屏障通透性研究  

Pharmacokinetics of a fusion protein for human acidic fibroblast growth factor and transcriptional activator protein in rat and its penetration across blood-brain barrier

作　　者：杨鹏辉[1] 许华[1] 张齐好[2] 李娟[1] 熊耀玲[1] 黄亚东[2] 苏志坚[2] 郑青[1] 

机构地区：[1]暨南大学药学院,广东广州510632 [2]暨南大学医药生物技术研究开发中心,广东广州510632

出　　处：《药学学报》2011年第10期1204-1208,共5页Acta Pharmaceutica Sinica

基　　金：国家"重大新药创制"科技重大专项资助项目(2009ZX09103-749);广东省重大科技专项"重大新药创制"课题(2011A080502014)

摘　　要：研究穿膜肽(transcriptional activator protein,TAT)和人酸性成纤维细胞生长因子(human acidicfibroblast growth factor,haFGF)融合蛋白TAT-haFGF14 154静脉注射(iv)后在大鼠血浆中的药代动力学特性,并探讨其在大鼠和小鼠体内血脑屏障的通透性,为阿尔茨海默症(Alzheimer’s disease,AD)的临床治疗用药提供依据。酶联免疫吸附实验(ELISA)检测静脉注射后TAT-haFGF14 154在大鼠血浆和小鼠脑匀浆液的含量,免疫组织化学法检测大鼠和小鼠脑中的分布。结果表明,大鼠单次颈静脉注射TAT-haFGF14 154 300μg.kg 1后,血药浓度-时间曲线符合二室开放模型,加权为1/C2,属于线性动力学消除,其中,分布半衰期为(0.049±0.03)h,消除半衰期为(0.55±0.05)h。结果提示,TAT-haFGF14 154在体内消除较快,可以迅速穿过血脑屏障,分布于大脑皮质和海马区,并定位于细胞核。This paper is to report the study of the pharmacokinetics of a fusion protein TAT-haFGF14 154 for human acidic fibroblast growth factor and transcriptional activator protein in rat plasma,and the investigation of their penetration across blood-brain barrier in mice and rats,in order to provide a basis for clinical development and treatment of Alzheimer＇s disease.Enzyme-linked immunosorbent assay（ELISA） was used to determine concentration of TAT-haFGF14 154 in rat plasma and in mouse brain homogenate;and immunohistochemistry was used to analyze the distribution in brain.The concentration-time curve fitted two-compartment open model which was linear kinetics elimination after a single intravenous injection of TAT-haFGF14 154 in rat at the dose of 300 μg kg 1.The half life time was 0.049 ± 0.03 h for distribution phase and 0.55 ± 0.05 h for elimination phase,and the weight was 1/C2.The result showed that TAT-haFGF14 154 could be detected in the brain by ELISA and immunohistochemistry,the elimination of TAT-haFGF14 154 in rat was swift,and TAT-haFGF14 154 could penetrate across the blood-brain barrier,distribute in pallium and hippocampus and locate in the nucleus.

关 键 词：穿膜肽 血脑屏障 药代动力学 酸性成纤维细胞生长因子 阿尔茨海默症 

分 类 号：R969.1[医药卫生—药理学]