肌生成抑制素(MSTN)抗体对肩袖撕裂后肌肉退变的治疗效果

The Treatment Efficacy of Myostatin Antibody Against Muscle Degeneration within the Torn Rotator Cuff in a Mouse Model

目的:探讨肌生成抑制素(MSTN)抗体对肩袖撕裂后肌肉萎缩、纤维化、脂肪浸润等肌肉退变的作用。方法:本研究共使用18只小鼠。其中,通过横切左肩冈上肌腱和肩胛上神经,建立12只小鼠巨大肩袖撕裂伴肌肉退变模型,术后3周,将12只小鼠随机分为注射MSTN抗体组(抗MSTN组,n=6)和注射磷酸缓冲盐溶液(PBS)组(PBS组,n=6),于左冈上肌撕裂部位分别注射MSTN抗体和PBS溶液,每周1次,共注射3周;另外6只仅切开皮肤和肌肉,未切断肌腱和神经的小鼠作为假手术组,不做任何注射。术后6周,取3组样本进行磁共振成像(MRI)检查,测量冈上肌肌肉重量、体积等指标,并进行HE染色、Masson染色,肌肉特异性环指蛋白1(MuRF1)和肌萎缩蛋白Fbox-1(Atrogin1)、磷酸化蛋白激酶(p-Akt)免疫组化染色等组织学分析。结果:抗MSTN组MRI上测量的冈上肌横截面积显著高于PBS组,但仍低于假手术组(P<0.001)。相较于PBS组,抗MSTN组的冈上肌肌肉重量、体积和肌纤维横截面积均更高(P<0.05),但仍低于假手术组;胶原沉积程度(P<0.001)和脂肪浸润面积(P<0.01)相较于PBS组更低,但仍高于假手术组。此外,抗MSTN组的MuRF1和Atrogin1表达显著低于PBS组,而p-Akt显著高于PBS组(P<0.001)。且抗MSTN组α-SMA表达阳性的肌成纤维细胞显著少于PBS组,但仍比假手术组高(P<0.001)。结论:使用MSTN抗体对肩袖撕裂后的肌萎缩、纤维化、脂肪浸润等肌肉退变有一定的抑制作用。

Objective To investigate the effect of myostatin(MSTN) antibody on muscle atrophy,fibrosis and fat infiltration in mice with rotator cuff tear. Methods A total of 18 mice were used in this study. By transecting supraspinatus tendon and suprascapular nerve on the left shoulder,the massive rotator cuff tear with muscle degeneration was induced in 12 mice. Three weeks later,the 12 mice were randomly divided into one group of 6,injected myostatin antibody(group anti-MSTN),and the other group of 6,injected phosphate buffered saline(PBS) once a week,for 3 weeks. Additionally,the rest six mice undergoing sham surgery served as the control(group sham) without any injection. Six weeks after the surgery,samples were collected and subjected to magnetic resonance imaging(MRI) examination, gross measurement, and histological analysis such as hematoxylin staining, Masson staining,muscle-specific RING finger protein 1(MuRF1),muscle-specific RING finger protein 1(Atrogin1),and phosphorylated Akt(p-Akt)immunohistochemical staining. Results The average cross-sectional area of the supraspinatus in group anti-myostatin was signficantly higher than group PBS,but still lower than the group sham in their MRI(P<0.001). Moreover,the average weight,volume and muscle fiber cross-sectional area of the former group were higher than group PBS,but lower than group sham(P<0.05). However,the average collagen deposition and fatty infiltration of the former were lower than that of group PBS(P<0.01),but higher than group sham. The average expression of MuRF1 and Atrogin1 of group anti-MSTN were significantly lower, while that of p-Akt was significantly higher than group PBS(P<0.001). Significantly less α-SMA was found in myofibroblasts of group anti-MSTN compared with group PBS,but significantly more compared with group sham(P<0.001). Conclusion Myostatin antibody has therapeutic potential against muslce degeneration such as muscle atrophy,fibrosis and fatty infiltration in the torn rotator cuff.