脑源性神经营养因子靶向药物的制备及其对阿耳茨海默转基因鼠的治疗作用

Preparation of brain-derived neurotrophic factor targeting drug and its therapeutic effect in Alzheimer's disease transgenic mice

目的:检测脑源性神经营养因子(BDNF)靶向药物对阿耳茨海默病(AD)转基因鼠的治疗作用。方法:将BDNF与抗胰岛素受体单克隆抗体(29B4)相结合,制备嵌合肽BDNF-PEG-29B4/SA。药物静脉注入AD转基因鼠tg2576体内,应用ELISA方法检测AD转基因鼠脑内BDNF的粥样蛋白(Aβ)的含量。结果:AD鼠脑内的BDNF浓度较高和平稳。可以有效降低AD转基因鼠脑内Aβ含量。结论:BDNF-PEG-29B4/SA可以通过主动转运进入血脑屏障,对AD转基因鼠有治疗作用。

Objective： To prepare a targeting drug for brain-derived neurotrophic factor （BDNF） and study its therapeutic effect in Alzheimer＇ s disease （AD） transgenic mice. Methods： The chimeric peptide （BDNF-PEG-29B4/SA） was prepared by binding BDNF to monoclonal antibody 29134 and intravenously injected into AD transgenic mice. The content of β-amyloid protein （ Aβ） in the brains of mice was determined by using enzyme-linked immunosorbent assay. Results： The concentration of BDNF remained high and stable in the brains of AD transgenic mice. The targeting drug significantly decreased the content of Aβ. Conclusion： BDNF targeting drug BDNF-PEG-29B4/SA can enter the blood-brain barrier by active transport and has a therapeutic effect in AD transgenic mice.