Pharmacological inhibition of myostatin improves skeletal muscle mass and function in a mouse model of stroke
Pharmacological inhibition of myostatin improves skeletal muscle mass and function in a mouse model of stroke
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DOI：
10.1038/s41598-017-13912-0
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发表时间：
2017-10-25
影响因子：
4.6
通讯作者：
Freyssenet, Damien Gilles
中科院分区：
文献类型：
--
作者：
Desgeorges, Marine Maud;Devillard, Xavier;Freyssenet, Damien Gilles
在中风患者中，骨骼肌质量的丧失会导致更长时间的虚弱和更低的康复效率。我们之前的研究表明，在中风小鼠模型中，骨骼肌负向调节因子--肌肉抑制素的表达显著增加。因此，我们验证了抑制肌肉生长抑制素可促进脑缺血后骨骼肌群和功能恢复的假说。右侧大脑中动脉闭塞(MCAO)造成大鼠脑缺血(45min)。瑞士雄性小鼠随机分为假手术组(n=10)、MCAO组(n=15)和MCAO组(n=12)，分别于术后即刻、MCAO后第3、7、10天皮下注射PINTA745。PINTA745减少了脑缺血后的体重损失，改善了体重恢复，以及肌肉力量和运动功能。PINTA745还促进了脑缺血15天后肌肉重量的恢复。从机制上讲，PINTA745-MCAO小鼠骨骼肌块的更好恢复与编码肌原纤维蛋白的基因表达增加有关。因此，抗肌肉抑制素策略可以促进脑缺血后骨骼肌的恢复，因此可能是对抗中风患者骨骼肌丢失和虚弱的一种有趣的策略。
In stroke patients, loss of skeletal muscle mass leads to prolonged weakness and less efficient rehabilitation. We previously showed that expression of myostatin, a master negative regulator of skeletal muscle mass, was strongly increased in skeletal muscle in a mouse model of stroke. We therefore tested the hypothesis that myostatin inhibition would improve recovery of skeletal muscle mass and function after cerebral ischemia. Cerebral ischemia (45 minutes) was induced by intraluminal right middle cerebral artery occlusion (MCAO). Swiss male mice were randomly assigned to Sham-operated mice (n = 10), MCAO mice receiving the vehicle (n = 15) and MCAO mice receiving an anti-myostatin PINTA745 (n = 12; subcutaneous injection of 7.5 mg.kg(-1) PINTA745 immediately after surgery, 3, 7 and 10 days after MCAO). PINTA745 reduced body weight loss and improved body weight recovery after cerebral ischemia, as well as muscle strength and motor function. PINTA745 also increased muscle weight recovery 15 days after cerebral ischemia. Mechanistically, the better recovery of skeletal muscle mass in PINTA745-MCAO mice involved an increased expression of genes encoding myofibrillar proteins. Therefore, an anti-myostatin strategy can improve skeletal muscle recovery after cerebral ischemia and may thus represent an interesting strategy to combat skeletal muscle loss and weakness in stroke patients.