中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (5): 1131-1137.doi: 10.4103/1673-5374.324853

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

异种脱细胞神经移植修复恒河猴全面神经缺损

  

  • 出版日期:2022-05-15 发布日期:2021-11-22

Repairing whole facial nerve defects with xenogeneic acellular nerve grafts in rhesus monkeys

Guo-Chen Zhu1, 2, *, Da-Jiang Xiao1, 2, *, Bi-Wen Zhu3, Yan Xiao4   

  1. 1Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical University, Wuxi, Jiangsu Province, China; 2Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Wuxi Clinical College of Nantong University, Wuxi, Jiangsu Province, China; 3College of Animal Science & Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong Province, China; 4Department of Pathology, Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, Jiangsu Province, China
  • Online:2022-05-15 Published:2021-11-22
  • Contact: Guo-Chen Zhu, MD, zgc2003doctor@njmu.edu.cn; Da-Jiang Xiao, dajiang2125@163.com.
  • Supported by:
    This work was financially supported by the National Natural Science Foundation of China, No. 81770990 (to GCZ); Jiangsu Provincial Key Research and Development Program of China, No. BE2018628 (to GCZ); Six Talent Peaks Project in Jiangsu Province of China, No. 2019-WSW-141 (to GCZ); Major Medicine Projects of Wuxi Health Commission of Jiangsu, China, No. Z201802 (to DJX); Precision Medicine Projects of Wuxi Health Commission of Jiangsu, China, No. J202002 (to GCZ).

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摘要：

化学萃取法制备的脱细胞异体神经移植在临床上用于桥接全面神经(颞骨外段面神经干-多分支区域)缺损，已取得了满意的效果。然而，临床治疗面神经缺损时异体供体的来源受到限制。实验暴露6只恒河猴的左侧颞外面神经干及其主要分支，解剖形成25 mm的间隙，构建左侧全面神经缺损猴模型，建模后随机分为2组，自体移植组3只采用猴同侧耳大神经即刻自体移植桥接修复，异种脱细胞神经移植组3只采用化学萃取法制备的小型猪异种脱细胞神经移植物即刻桥接修复。术后8个月，通过面部对称性恢复评估、神经肌肉电生理测试、标记神经示踪剂逆行运输、再生神经和靶肌肉形态学评价显示，两组猴在静态时面部均对称，但在面部运动时略微不对称，并且可以主动完全闭合眼睑。两组猴面神经瘫痪的恢复程度均达到House-Brackmann II级。每只猴的手术侧可记录到复合肌肉动作电位和口轮匝肌对电刺激的反应。在每只猴损伤侧面神经核内可检测到一些荧光金标记的神经元。免疫组织化学染色结果显示，再生神经中可见丰富的神经丝200(NF-200)阳性表达的神经元轴突和可溶性蛋白100(S-100)阳性表达的许旺细胞。亚甲蓝染色和透射电子显微镜染色显示，移植物中段有大量有髓神经元轴突。上述数据说明，小型猪异种脱细胞神经修复恒河猴的全面神经缺损是安全有效的，与自体神经移植效果相似。因此，在没有其他修复方法的情况下，应用异种脱细胞神经桥接全面神经缺损可能是一个合适的选择。

https://orcid.org/0000-0003-4814-1550 (Guo-Chen Zhu); https://orcid.org/0000-0002-8085-9274 (Da-Jiang Xiao)

关键词: 脱细胞神经, 复合肌肉动作电位, 面神经缺损, 面部对称性, 猴, 神经移植, 神经再生, 逆行标记试验, 突触素, 异种

Abstract: Acellular nerve allografts conducted via chemical extraction have achieved satisfactory results in bridging whole facial nerve defects clinically, both in terms of branching a single trunk and in connecting multiple branches of an extratemporal segment. However, in the clinical treatment of facial nerve defects, allogeneic donors are limited. In this experiment, we exposed the left trunk and multiple branches of the extratemporal segment in six rhesus monkeys and dissected a gap of 25 mm to construct a monkey model of a whole left nerve defect. Six monkeys were randomly assigned to an autograft group or a xenogeneic acellular nerve graft group. In the autograft group, the 25-mm whole facial nerve defect was immediately bridged using an autogenous ipsilateral great auricular nerve, and in the xenogeneic acellular nerve graft group, this was done using a xenogeneic acellular nerve graft with trunk-branches. Examinations of facial symmetry, nerve-muscle electrophysiology, retrograde transport of labeled neuronal tracers, and morphology of the regenerated nerve and target muscle at 8 months postoperatively showed that the faces of the monkey appeared to be symmetrical in the static state and slightly asymmetrical during facial movement, and that they could actively close their eyelids completely. The degree of recovery from facial paralysis reached House-Brackmann grade II in both groups. Compound muscle action potentials were recorded and orbicularis oris muscles responded to electro-stimuli on the surgical side in each monkey. FluoroGold-labeled neurons could be detected in the facial nuclei on the injured side. Immunohistochemical staining showed abundant neurofilament-200-positive axons and soluble protein-100-positive Schwann cells in the regenerated nerves. A large number of mid-graft myelinated axons were observed via methylene blue staining and a transmission electron microscope. Taken together, our data indicate that xenogeneic acellular nerve grafts from minipigs are safe and effective for repairing whole facial nerve defects in rhesus monkeys, with an effect similar to that of autologous nerve transplantation. Thus, a xenogeneic acellular nerve graft may be a suitable choice for bridging a whole facial nerve defect if no other method is available. The study was approved by the Laboratory Animal Management Committee and the Ethics Review Committee of the Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical University, China (approval No. 2018-D-1) on March 15, 2018.

Key words: acellular nerve, compound muscle action potentials, facial nerve defect, facial symmetry, monkey, nerve graft, nerve regeneration, retrograde labeling test, synaptophysin, xenogeneic

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