E8002 Inhibits Peripheral Nerve Adhesion by Enhancing Fibrinolysis of L-Ascorbic Acid in a Rat Sciatic Nerve Model
E8002 Inhibits Peripheral Nerve Adhesion by Enhancing Fibrinolysis of L-Ascorbic Acid in a Rat Sciatic Nerve Model
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DOI：
10.3390/ijms21113972
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发表时间：
2020-06-01
影响因子：
5.6
通讯作者：
Uchikado, Hisaaki
中科院分区：
文献类型：
--
作者：
Kikuchi, Kiyoshi;Setoyama, Kentaro;Uchikado, Hisaaki
神经周围粘连导致神经病变是周围神经手术最不希望的后果之一。然而，目前在周围神经外科领域中没有广泛使用的具有抗粘连作用的化合物。E8002是一种新型的抗粘连多层膜，含有L-抗坏血酸（AA）。本研究旨在探讨E8002在大鼠坐骨神经粘连模型中的作用及其机制。共使用21只大鼠。术后6周，与E8002 AA（-）组（粘连手术后使用E8002膜包裹神经，不包括AA）和粘连组（粘连手术但未治疗）相比，E8002组（粘连手术后使用E8002膜包裹神经）的宏观粘连评分显著较低。相应地，显微镜检查显示E8002 AA（-）和粘连组中有明显的瘢痕组织。此外，使用人血液样本的体外研究表明，AA增强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和纤溶调节发挥抗粘附作用。
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.