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E8002 通过增强 l-抗坏血酸的纤溶作用抑制大鼠坐骨神经模型中的外周神经粘连。

E8002 Inhibits Peripheral Nerve Adhesion by Enhancing Fibrinolysis of l-Ascorbic Acid in a Rat Sciatic Nerve Model.

机构信息

Division of Brain Science, Department of Physiology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.

Department of Neurosurgery, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.

出版信息

Int J Mol Sci. 2020 Jun 1;21(11):3972. doi: 10.3390/ijms21113972.

Abstract

Perineural adhesions leading to neuropathy are one of the most undesirable consequences of peripheral nerve surgery. However, there are currently no widely used compounds with anti-adhesive effects in the field of peripheral nerve surgery. E8002 is a novel, anti-adhesive, multi-layer membrane that contains L-ascorbic acid (AA). Here, we investigated the effect and mechanism of E8002 in a rat sciatic nerve adhesion model. A total of 21 rats were used. Six weeks after surgery, macroscopic adhesion scores were significantly lower in the E8002 group (adhesion procedure followed by nerve wrapping with E8002) compared to the E8002 AA(-) group (adhesion procedure followed by nerve wrapping with the E8002 membrane excluding AA) and adhesion group (adhesion procedure but no treatment). Correspondingly, a microscopic examination revealed prominent scar tissue in the E8002 AA(-) and adhesion groups. Furthermore, an in vitro study using human blood samples showed that AA enhanced tissue-type, plasminogen activator-mediated fibrinolysis. Altogether, these results suggest that E8002 may exert an anti-adhesive action via AA and the regulation of fibrinolysis.

摘要

神经周围粘连导致神经病变是周围神经手术最不理想的后果之一。然而,目前在周围神经手术领域还没有广泛使用具有抗粘连作用的化合物。E8002 是一种新型的、具有抗粘连作用的多层膜,其中含有 L-抗坏血酸(AA)。在这里,我们研究了 E8002 在大鼠坐骨神经粘连模型中的作用和机制。总共使用了 21 只大鼠。手术后 6 周,E8002 组(粘连手术后用 E8002 包裹神经)的宏观粘连评分明显低于 E8002AA(-)组(粘连手术后用不含 AA 的 E8002 膜包裹神经)和粘连组(粘连手术但不治疗)。相应地,显微镜检查显示 E8002AA(-)和粘连组有明显的疤痕组织。此外,使用人血样本进行的体外研究表明,AA 增强了组织型、纤溶酶原激活物介导的纤维蛋白溶解。总之,这些结果表明 E8002 可能通过 AA 和纤维蛋白溶解的调节发挥抗粘连作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38e9/7313081/e0ad35b96dd4/ijms-21-03972-g001.jpg

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