超声微泡对移植骨髓间充质干细胞跨血脑屏障迁移的作用及其机制

Previous research found that ultrasonic microbubble could safely、effectively、reversibly open the blood brain barrier,promot the macromolecule drug transporting bypass the blood brain barrier.Our previous experiment found that ultrasonic microbubble could open the blood brain barrier,promot the Bone marrow mesenchyal stem cells transporting to brain parenchyma bypass the blood brain barrier.In order to study the effection and mechanism,In this topic,we plan to establish the blood brain barrier model in vitro and rat forebrain ischemic/refusion model,using immunoflurescence labelling、immunoblotting、in situ hybridization、electron microscope、tissue staining et,to observe the effection between ultrasonic microbubble openning the blood brain barrier and the tansplantation cells by vein migrating to brain parenchyma.also approaching the relationship between morphologic change、sturctural protein expression、adhsion molecule VCAM-1 expression,as well as the effection of ultrosonic microbabble to Ca2＋/CaM path、Akt path 、PKC path.Which can wish to clarify the effection and mechanism on ultrosonic microbubble to Bone marrow mesenchyal stem cells transporting to brain parenchyma bypass the blood brain barrier,which may provide rationale and experiment evidence to search a new method whin can effectively enhanc the effection to stem cells using to therapy injured brain.

既往研究发现超声微泡可安全、有效、可逆开放血脑屏障，促进大分子药物跨血脑屏障转运。我们前期实验发现超声微泡开放血脑屏障也能促进经静脉移植骨髓间充质干细胞向脑实质的迁移,为进一步研究其作用及机制，本课题拟体外建立血脑屏障模型和体内建立大鼠前脑缺血/再灌注模型，应用免疫荧光标记、免疫印迹、原位杂交、电镜、组织染色等方法，观察超声微泡开放血脑屏障对经静脉移植细胞向脑实质迁移的影响，并探讨与血脑屏障形态变化、血脑屏障结构蛋白表达改变、血脑屏障黏附分子VCAM-1表达改变的关系，以及超声微泡对Ca2＋/CaM通路、Akt通路、PKC通路的作用。有望阐明超声微泡对骨髓间充质干细胞跨血脑屏障向脑实质区迁移的作用及机制，为寻找一种有效增强干细胞移植治疗脑损伤作用的新方法提供理论基础和实验依据。