Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, PR China.
Aging (Albany NY). 2021 Mar 10;13(6):8454-8466. doi: 10.18632/aging.202655.
In this study, we investigated the beneficial effects of high endogenous levels of n-3 polyunsaturated fatty acids (PUFAs) on skeletal muscle repair and regeneration using a mouse cardiotoxin (CTX, 20 μM/200 μL) -induced gastrocnemius muscle injury model. Transgenic mice expressing the gene, encoding n-3 fatty acid desaturase, showed higher n-3 PUFA levels and lower n-6/n-3 PUFA ratios in gastrocnemius muscle tissues. Hematoxylin and eosin and Masson's trichrome staining of gastrocnemius sections revealed increased muscle fiber size and reduced fibrosis in mice on days 7 and 14 after CTX injections. Gastrocnemius muscle tissues from mice showed reduced inflammatory responses and increased muscle fiber regeneration reflecting enhanced activation of satellite cells on day 3 after cardiotoxin injections. Gastrocnemius muscle tissues from cardiotoxin-treated mice showed reduced levels of pro-apoptotic proteins (Caspase 3 and Bax) and increased levels of anti-apoptotic proteins (Bcl-2 and Survivin). Moreover, eicosapentaenoic acid (EPA) reduced the incidence of apoptosis among cardiotoxin-treated C2C12 mouse myoblasts. These findings demonstrate that higher endogenous n-3 PUFA levels in mice enhances skeletal muscle repair and regeneration following cardiotoxin-induced injury.
在这项研究中，我们使用小鼠心脏毒素（CTX，20 μM/200 μL）诱导的比目鱼肌损伤模型，研究了内源性高水平 n-3 多不饱和脂肪酸（PUFA）对骨骼肌修复和再生的有益作用。表达 n-3 脂肪酸去饱和酶基因的转基因小鼠在比目鱼肌组织中表现出更高的 n-3 PUFA 水平和更低的 n-6/n-3 PUFA 比值。CTX 注射后 7 天和 14 天，比目鱼肌切片的苏木精和伊红以及 Masson 三色染色显示，基因敲入小鼠的肌纤维大小增加，纤维化减少。CTX 注射后 3 天，基因敲入小鼠的比目鱼肌组织中炎症反应减少，肌纤维再生增加，反映出卫星细胞的激活增强。心脏毒素处理的基因敲入小鼠的比目鱼肌组织中促凋亡蛋白（Caspase 3 和 Bax）水平降低，抗凋亡蛋白（Bcl-2 和 Survivin）水平升高。此外，二十碳五烯酸（EPA）降低了心脏毒素处理的 C2C12 小鼠成肌细胞的凋亡发生率。这些发现表明，基因敲入小鼠内源性 n-3 PUFA 水平的升高增强了心脏毒素诱导损伤后骨骼肌的修复和再生。
