论文部分内容阅读
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。
To investigate the pharmacokinetic properties of TAT-haFGF fusion protein TAT-haFGF14 154 in rat plasma after intravenous injection (iv) , And to explore its permeability in the blood-brain barrier in rats and mice to provide a basis for clinical treatment of Alzheimer’s disease (AD). Enzyme-linked immunosorbent assay (ELISA) was used to detect the content of TAT-haFGF14 154 in rat plasma and mouse brain homogenate after intravenous injection. The distribution of TAT-haFGF14 154 in rat and mouse brain was detected by immunohistochemistry. The results showed that after a single jugular vein injection of TAT-haFGF14 154 300 μg · kg -1, the plasma concentration-time curve conformed to the two-compartment open model with a weight of 1 / C2, which belongs to the linear kinetic elimination. The distribution half-life was 0.049 ± 0.03) h, the elimination half-life was (0.55 ± 0.05) h. The results suggest that TAT-haFGF14 154 is rapidly eliminated in vivo and can rapidly cross the blood-brain barrier and distribute in the cerebral cortex and hippocampus and locate in the nucleus.