脂质体包埋脑源性神经营养因子靶向透过血脑屏障

Liposome-encapsulated brain-derived neurotrophic factor targets blood-brain barrier

目的:对脂质体包埋脑源性神经营养因子进行一定的修饰,观察其透过血脑屏障的组织分布特点。方法:选取西安外事学院医学院进行实验的SD大鼠32只作为研究对象,随机数字法分为脂质体组(n=16)和对照组(n=16)。建立AD大鼠模型,对照组大鼠不给予任何处理,脂质体组经大鼠尾静脉注射10μg/kg Tf-p GFAP-BDNF-PEG,分析脂质体包埋脑源性神经营养因子靶向脂质体透过血脑屏障的组织分布特点。结果:采用24m Ci99m TC标记1 ml神经生长因子,取20μl上柱分离后采集40~50管收集液,每管0.5 ml,测定放射性技术。将峰所在的8~17管收集液混合回收,结果显示神经营养因子标记率为98.9%。脂质体组第10、14天脑源性神经营养因子免疫阳性表达细胞数,显著高于对照组(P<0.05);脂质体组大鼠脑组织中神经营养因子的基因表达第14天时,显著高于对照组(P<0.05);脂质体组大鼠存在神经营养因子表达,并且神经营养因子表达水平显著高于对照组(P<0.05)。肉眼观察所采脑脊液清亮、无色、透明,且显微镜下未检出红细胞。脂质体组大鼠脑脊液便隐血胶体金检测结果显示阴性,对照组为阳性。结论:转铁蛋白联合聚乙二醇修饰的脂质体合并连接脑特异性启动子,能提高脂质体靶向性。

Objective To observe the characteristics of the tissue distribution of the blood brain barrier through the modification of the liposome encapsulated brain derived neurotrophic factor. Methods： A total of 32 SD rats were selected from Xi＇an Medicine College of Foreign Affairs as the research object,and randomly divided into two groups （ n = 16 ） and control group （ n = 16 ） . To establish a rat model of AD rats in the control group received no treatment,liposome group by rat tail vein injection of 10 滋 g/kg Tf- pGFAP-BDNF-PEG,analysis of liposome entrapped BDNF targeting liposomes through blood brain barrier tissue distribution characteristics. Results ： 4 0 -5 0 nerve growth factor （1 ml） was collected by using 24mCi99mTC and 20 L 0. 5 ml was collected on the top of the column. The concentration of 8-17 tube in the peak was recovered,and the results showed that the labeling rate of neurotrophic factor was 98. 9% . Liposome group for tenth days,14 days of BDNF immunoreactive cells,significantly higher than the control group （ P〈0. 05） ;neurotrophic factor in brain tissue of rats in body lipid gene expression at day fourteenth,significantly higher than the control group （ P〈0. 05） ;expression of neurotrophic factors in liposome group rat,and neurotrophic factor expression level was significantly higher than the control group （ P 〈 0 .0 5 ） . The cerebrospinal fluid was clear, colorless and transparent, and no red blood cells were detected under microscope. Liposome group in cerebrospinal fluid of rats with fecal occult blood detection results of gold colloid showed negative,while the control group was positive. Conclusion： The combination of transferrin and polyethylene glycol modified liposomes combined with brain specific promoter can improve the targeting of liposomes.