PTD介导蛋白通过血脑屏障及其在脑组织中的分布

目的：探讨HIV－1 TAT的蛋白转导结构域（protein transduction domain,PTD）介导的大分子蛋白通过血脑屏障（blood-brain barrier,BBB）的作用及其在脑组织中的分布。方法：将纯化的PTD－BCR／ABL融合蛋白及伊文思蓝经尾静脉注入小鼠体内，制备全脑组织恒冷箱连续切片，用免疫组织化学染色法检测PTD－BCR／ABL融合蛋白在脑组织中的分布，用伊文思蓝作为指示剂检测PTD对BBB开放的影响。结果：将其注射到小鼠体内后，在全脑组织细胞中均检测到PTD－BCR／ABL融合蛋，呈非特异性组织分布；全脑组织除无BBB区域外，余脑区均无伊文思蓝渗入，PTD不引起BBB的开放。结论：PTD可在体内特异性介导大分子蛋白通过血脑屏障，并在全脑组织细胞中分布，为肽类或蛋白类大分子药物通过BBB进入中枢神经系统（central nervous ystern,CNS)开辟了一条新的途径。

Delivery of Macromolecular Protein Across Blood-brain Barrier into Brain and Its Distribution in Brain Mediated by PTD

Objective:To explore the delivery of macromolecular protein across blood-brain barrier (BBB) into brain and its distribution in brain mediated by protein transduction domain (PTD) of HIV-1 TAT.Methods: The purified PTD-BCR/ABL fusion protein as well as Evans blue were injected into mice through caudal vein and the cryostat sections of brain tissue were prepared. The distribution of PTD-BCR/ABL fusion protein in brain tissue was observed by immunohistochemistry staining and the in fluenceon BBB opening by PTD was observed with Evans blue as a indicator. Results:PTD-BCR/ABL fusion protein was detected in full brain tissue after intravenous injection of it and it's distribution in brain tissue was not specific. No Evans blue was detected in full brain except of the regions without BBB, and PTD didn't induce BBB opening.Conclusion: PTD can transport macromolecular protein into full brain tissue across BBB in vivo. It provides a novel approach for the delivery of macromolecular peptide or protein drags into central nervous system.