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病毒载体传递卵泡抑素增强了神经再支配肌肉的恢复。

Viral vector delivery of follistatin enhances recovery of reinnervated muscle.

机构信息

Division of Hand Surgery, Department of Orthopaedic Surgery, Virginia Commonwealth University Medical Center, Richmond, Virginia.

Divison of Plastic Surgery, Department of General Surgery, Virginia Commonwealth University Medical Center, Richmond, Virginia.

出版信息

Muscle Nerve. 2019 Oct;60(4):474-483. doi: 10.1002/mus.26653. Epub 2019 Aug 14.

Abstract

INTRODUCTION

Poor recovery following nerve repair is due to progressive temporal loss of muscle function. Follistatin (FS), a glycoprotein with anabolic properties, may enhance muscle recovery following reinnervation.

METHODS

Seventy-two male Sprague-Dawley rats underwent temporary (3 or 6 month) denervation or sham denervation. After reinnervation, rats were administered adeno-associated viral vectors expressing FS deoxyribonucleic acid (isoform FS-317) injected into the target muscle or sham treatment. Final assessment included muscle function testing, muscle histomorphology, nerve histomorphology, and FS protein quantification.

RESULTS

FS improved muscle mass and type IIB muscle fiber size, and increased G-ratios and mean axon diameter in the 6-month temporary denervation group (P < .05). Elevated FS protein levels were detected in treated muscle (P < .05). FS increased satellite cell counts following temporary denervation and repair (P < .05).

DISCUSSION

FS treatment had anabolic, neurotrophic, and satellite cell stimulatory effects when administered following prolonged (6-month) temporary denervation and repair.

摘要

简介

神经修复后恢复不佳是由于肌肉功能逐渐丧失。卵泡抑素(FS)是一种具有合成代谢特性的糖蛋白,可能会增强神经再支配后的肌肉恢复。

方法

72 只雄性 Sprague-Dawley 大鼠接受了暂时性(3 或 6 个月)去神经支配或假去神经支配。神经再支配后,将表达 FS 脱氧核糖核酸(FS-317 同工型)的腺相关病毒载体注射到目标肌肉中进行治疗,或进行假处理。最终评估包括肌肉功能测试、肌肉组织形态学、神经组织形态学和 FS 蛋白定量。

结果

FS 改善了 6 个月暂时性去神经支配组的肌肉质量和 IIB 型肌纤维大小,并增加了 G 比和平均轴突直径(P<0.05)。在治疗的肌肉中检测到 FS 蛋白水平升高(P<0.05)。FS 增加了暂时性去神经支配和修复后的卫星细胞计数(P<0.05)。

讨论

FS 治疗在接受长期(6 个月)暂时性去神经支配和修复后具有合成代谢、神经营养和卫星细胞刺激作用。

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