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Astragoloside IV Loaded Polycaprolactone Membrane Repairs Blood Spinal Cord Barrier and Recovers Spinal Cord Function in Traumatic Spinal Cord Injury.
Journal of Biomedical Nanotechnology ( IF 2.9 ) Pub Date : 2019-3-8 , DOI: 10.1166/jbn.2019.2715
Di Zhang , Quan Wang , Sheng Wang , Yixing Huang , Naifeng Tian , Yan Wu , Yaosen Wu , Yifei Zhou , Huazi Xu , Xiaolei Zhang

Traumatic Spinal Cord Injury (SCI) is a serious challenge of CNS which may oftenly result in permanent paralysis and disability. The disruption of blood spinal cord barrier (BSCB) is a major step in the secondary injury of SCI. Until recently there are no restorative therapies for traumatic SCI. BSCB is considered to be a therapeutic target for SCI, however few biomaterials have been developed to restore the disrupted BSCB in SCI. In this study, an AST-PCL membrane was fabricated with a steady release of Astragoloside IV (AST) and its effects on BSCB repair as well as the functional recovery of SCI were evaluated. Firstly, this study demonstrated that AST-PCL (polycaprolactone) degradation media protects endothelial cells from apoptosis by down-regulating the expression of cleaved Caspase 3 and decreasing the ratio of Bax/Bcl-2, it also attenuates the stress fiber formation in vitro. Secondly, the rat model of traumatic SCI showed that AST-PCL treatment inhibits the disruption of BSCB permeability, as detected by MRI, Evan's Blue extravasation and water content. Thirdly, this study found that AST-PCL up-regulates the level of tight junction proteins including Occludin, Claudin5 and ZO-1. Furthermore, it is also demonstrated that AST-PCL treatment down-regulates Matrix metalloproteinase-9 secretion and diminishes neutrophil infiltration. Finally, this study found that AST-PCL treatment could significantly inhibit apoptosis, decrease tissue damage and improve functional recovery in SCI rats. Taken together, this study shows that AST-PCL might be an efficient biomaterial for BSCB repair and a potential drug therapy for SCI.

中文翻译:

载有黄芪甲苷IV的聚己内酯膜可修复血液脊髓屏障,并在创伤性脊髓损伤中恢复脊髓功能。

脊髓性脊髓损伤(SCI)是中枢神经系统的严重挑战,可能经常导致永久性瘫痪和残疾。血脊髓屏障(BSCB)的破坏是SCI继发性损伤的重要步骤。直到最近,还没有针对创伤性SCI的修复疗法。BSCB被认为是SCI的治疗靶标,但是很少有生物材料能够恢复SCI中被破坏的BSCB。在这项研究中,制备了稳定释放的黄芪甲苷IV(AST)的AST-PCL膜,并评估了其对BSCB修复以及SCI功能恢复的作用。首先,这项研究证明AST-PCL(聚己内酯)降解培养基可通过下调裂解的Caspase 3的表达并降低Bax / Bcl-2的比例来保护内皮细胞免于凋亡,体外。其次,创伤性脊髓损伤的大鼠模型显示,AST-PCL处理可抑制BSCB通透性的破坏,如MRI,Evan's Blue外渗和含水量所检测。第三,这项研究发现AST-PCL上调了紧密连接蛋白(包括Occludin,Claudin5和ZO-1)的水平。此外,还证明了AST-PCL处理下调了基质金属蛋白酶9的分泌并减少了中性粒细胞的浸润。最后,这项研究发现AST-PCL处理可以显着抑制SCI大鼠的细胞凋亡,减少组织损伤并改善功能恢复。两者合计,这项研究表明AST-PCL可能是BSCB修复的有效生物材料和SCI的潜在药物治疗。
更新日期:2020-08-21
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