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同种异体移植联合全身 FK506 比导管植入在大鼠坐骨神经损伤模型中产生更大的功能恢复。

Allografting combined with systemic FK506 produces greater functional recovery than conduit implantation in a rat model of sciatic nerve injury.

机构信息

Medical Center Clinic, CMFS, Neuroscience, Bremen, Germany.

出版信息

J Reconstr Microsurg. 2010 Feb;26(2):123-9. doi: 10.1055/s-0029-1243297. Epub 2009 Dec 10.

DOI:10.1055/s-0029-1243297
PMID:20013591
Abstract

Implantation of allografts or nerve conduits has been used to promote regeneration following peripheral nerve injuries involving substantial axon loss. Both methods provide promising alternatives to autologous grafting and avoid donor site morbidity. We compared the relative efficacies of allografting versus conduit implantation in a rat model of sciatic nerve regeneration. Two rat strains (Lewis and Dark Agouti; n = 30) were employed. Unoperated animals served as controls (group I). Animals in groups II and III underwent left sciatic nerve resection over a distance of 15 mm; group II animals received implants of collagen type I conduits; and group III animals received allografts from the other rat strain and systemic low-dose (0.1 mg/kg/d) administration of FK506. Walking tracks were recorded after 4, 8, 12, and 16 weeks; nerve sections were stained for myelin basic protein after 16 weeks. Functional tests revealed significantly better recovery in group III animals compared with group II even though there was no significant difference in the extent of remyelination. Neither group achieved the functional or histomorphometric values of control animals. Improved functional recovery following allografting plus systemic FK506, in comparison with conduit implantation, underlines the importance of systemic administration of neurotrophic molecules for nerve regeneration.

摘要

同种异体移植物或神经导管的植入已被用于促进周围神经损伤后的再生,这些损伤涉及大量轴突丢失。这两种方法都为自体移植物提供了有前途的替代方案,并避免了供体部位的发病率。我们在大鼠坐骨神经再生模型中比较了同种异体移植物与导管植入的相对疗效。使用了两种大鼠品系(Lewis 和 Dark Agouti;n = 30)。未手术动物作为对照(第 I 组)。第 II 组和第 III 组动物接受了 15mm 长的左侧坐骨神经切除术;第 II 组动物接受了 I 型胶原导管植入;第 III 组动物接受了来自另一种大鼠品系的同种异体移植物和全身低剂量(0.1mg/kg/d)FK506 给药。在 4、8、12 和 16 周后记录行走轨迹;在 16 周后对神经切片进行髓鞘碱性蛋白染色。功能测试显示,第 III 组动物的恢复明显优于第 II 组,尽管在髓鞘再生程度上没有显著差异。两组均未达到对照动物的功能或组织形态计量学值。与导管植入相比,同种异体移植加全身 FK506 后的功能恢复改善,强调了全身给予神经营养分子对神经再生的重要性。

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J Orthop Surg Res. 2024 Dec 19;19(1):859. doi: 10.1186/s13018-024-05343-1.
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Use of FK506 and bone marrow mesenchymal stem cells for rat hind limb allografts.FK506 和骨髓间充质干细胞在大鼠后肢同种异体移植中的应用。
Neural Regen Res. 2012 Dec 5;7(34):2681-8. doi: 10.3969/j.issn.1673-5374.2012.34.005.
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Tacrolimus reduces scar formation and promotes sciatic nerve regeneration.
他克莫司可减少瘢痕形成,促进坐骨神经再生。
Neural Regen Res. 2012 Nov 15;7(32):2500-6. doi: 10.3969/j.issn.1673-5374.2012.32.003.
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Effect of FK506 in reducing scar formation by inducing fibroblast apoptosis after sciatic nerve injury in rats.FK506 通过诱导坐骨神经损伤后成纤维细胞凋亡减少瘢痕形成的作用。
Cell Death Dis. 2013 Mar 7;4(3):e526. doi: 10.1038/cddis.2013.56.