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缓释雷帕霉素涂层仿生周围神经支架促进大鼠损伤坐骨神经的再生。

Slow-releasing rapamycin-coated bionic peripheral nerve scaffold promotes the regeneration of rat sciatic nerve after injury.

机构信息

Department of Anatomy, Histology and Embryology, The Fourth Military Medical University, Xi'an 710032, PR China.

Institute of Orthopedics, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, PR China.

出版信息

Life Sci. 2015 Feb 1;122:92-9. doi: 10.1016/j.lfs.2014.12.005. Epub 2014 Dec 19.

Abstract

AIMS

To investigate the effect of locally slow-released rapamycin (RAPA) from the bionic peripheral nerve scaffold on rat sciatic nerve regeneration in the early phase of nerve injury.

MAIN METHODS

Slow-releasing RAPA-polyhydroxy alcohol (PLGA) microspheres were prepared and tested for microsphere diameter and slow-release effect in vitro after loading onto nerve scaffold. A total of 48 male SD rats were randomly divided into control group and 3 experimental groups as follows: group 1: RAPA-PLGA scaffold; group 2: RAPA scaffold; and group 3: scaffold alone. In the control group, a 15mm sciatic nerve was excised and religated reversely. In the experimental groups, the scaffolds were used to bridge a defect of 15mm sciatic nerve. The outcome of nerve regeneration was evaluated using neurophysiological and neuromuscular morphological techniques.

KEY FINDINGS

The RAPA-PLGA microspheres displayed a smooth exterior. The slow-release of RAPA in group 1 lasted for 14days. The sciatic nerve function index (SFI) and electrophysiological and morphological features were examined 12weeks after the surgery in all groups to reveal various degrees of ipsilateral sciatic nerve regeneration. The SFI values at 12weeks showed no significant difference between the RAPA-PLGA scaffold and control groups; morphological observations revealed that the outcomes of nerve regeneration in the above 2 groups were similar and significantly better than those in the RAPA scaffold and scaffold alone groups.

SIGNIFICANCE

RAPA-PLGA microsphere-loaded bionic peripheral nerve scaffold gradually released RAPA locally in the early phase of sciatic nerve regeneration, reduced the secondary nerve injury, and evidently promoted the regeneration of peripheral nerve.

摘要

目的

研究仿生周围神经支架中局部缓慢释放的雷帕霉素(RAPA)对大鼠损伤神经早期坐骨神经再生的影响。

方法

将 RAPA 载入神经支架后,在体外对慢释放 RAPA-聚乙醇酸(PLGA)微球进行微球直径和慢释放效果的测试。将 48 只雄性 SD 大鼠随机分为对照组和 3 个实验组,如下:组 1:RAPA-PLGA 支架;组 2:RAPA 支架;组 3:单独支架。在对照组中,反向切除 15mm 坐骨神经并重新连接。在实验组中,使用支架桥接 15mm 坐骨神经缺损。采用神经生理和神经肌肉形态学技术评估神经再生的结果。

主要发现

RAPA-PLGA 微球表面光滑。组 1 中的 RAPA 缓慢释放持续了 14 天。所有组在手术后 12 周检查坐骨神经功能指数(SFI)和电生理及形态特征,以显示不同程度的同侧坐骨神经再生。12 周时 SFI 值在 RAPA-PLGA 支架和对照组之间无显著差异;形态学观察显示,上述 2 组的神经再生结果相似,明显优于 RAPA 支架和单独支架组。

意义

负载 RAPA-PLGA 微球的仿生周围神经支架在坐骨神经再生的早期阶段局部缓慢释放 RAPA,减少了二次神经损伤,明显促进了周围神经的再生。

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