纳米基因载体RGD-DMAPA-Amyp负载HIF-1α靶向递送至缺血性脑卒中损伤内皮细胞促血管新生

缺血性脑卒中治疗的重点是建立侧支循环，促进受损神经组织修复。靶向选择内皮细胞是治疗脑缺血损伤的关键。RGD肽作为整合素的配体能特异结合缺血缺氧损伤时缺血内皮细胞表达增高的整合素位点，是特异的内皮细胞靶向因子。本课题组前期工作证实，骨髓间充质干细胞经低氧诱导因子HIF-1α基因修饰后，分泌VEGF等促血管新生因子的能力增强，能促进脑缺血内皮细胞新生及受损的神经功能修复。本研究在设计合成偶联内皮靶向因子RGD肽的新型纳米基因载体RGD-DMAPA-Amyp的基础上，拟负载HIF-1α基因靶向递送至脑缺血损伤区内皮细胞，体内从脑卒中模型的神经功能行为学、脑灌注MRI、血管新生检测，研究其对脑缺血损伤的促血管新生作用；体外检测纳米基因载体的表观性能及对损伤的脑血管内皮细胞靶向转染效果和血管新生作用，深入阐明基因递送机制和其对神经损伤的修复，提高缺血性脑卒中的治疗效果，为临床治疗提供坚实的科学依据

Ischemic stroke treatment is focused on the establishment of collateral circulation and promote the repair of damaged nerve tissue. Select targeting endothelial cells The key treatment of cerebral ischemic injury. RGD peptides as integrin ligands specific binding when endothelial cell injury by hypoxia ischemia table Integrin sites of increased, the specific endothelial cell targeting factor. Our previous work demonstrated that bone marrow mesenchymal stem cells.After the cells by hypoxia-inducible factor HIF-1α gene modification, the ability to secrete angiogenic factors VEGF and other enhancements, promote cerebral ischemia.Endothelial cell regeneration and repair of damaged nerve function. This study was designed and synthesized in endothelial coupling factor RGD peptides targeting new nano .Gene targeting vector basis RGD-DMAPA-Amyp on the proposed load HIF-1α gene targeted delivery to ischemic brain damage endothelial cells .Cells, in vivo models of stroke from neurological behavior of learning, brain perfusion MRI, angiogenesis testing study on cerebral ischemic injury.The role of angiogenesis apparent in vitro assay performance nano gene targeting vector and damage brain endothelial cell targeting turn.Transfection efficiency and angiogenesis, elucidate gene delivery mechanisms and its repair nerve damage, and improve the treatment of ischemic stroke provide a solid scientific basis for clinical treatment.