A Soluble Activin Receptor IIB Fails to Prevent Muscle Atrophy in a Mouse Model of Spinal Cord Injury
A Soluble Activin Receptor IIB Fails to Prevent Muscle Atrophy in a Mouse Model of Spinal Cord Injury
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DOI：
10.1089/neu.2015.4058
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发表时间：
2016-06-15
影响因子：
4.2
通讯作者：
Cardozo, Christopher P.
中科院分区：
文献类型：
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作者：
Graham, Zachary A.;Collier, Lauren;Cardozo, Christopher P.
肌肉生长抑制素（MST）是肌肉生长和大小的有效调节剂。脊髓损伤（SCI）导致损伤水平以下的肌肉明显萎缩。目前，没有有效的药物治疗可用于预防SCI后的病灶下肌肉萎缩。为了确定用可溶性激活素IIB受体（RAP-031）抑制MST是否防止病灶下SCI诱导的肌肉萎缩，将小鼠随机分配到以下组：假手术-SCI; SCI+媒介物组（SCI-VEH）;和SCI+RAP-031（SCI-RAP-031）。脊髓损伤是通过在胸10级完全横断诱导的。在术后56天对动物实施安乐死。RAP-031减少但不阻止SCI后体重减轻。与SCI-VEH相比，RAP-031增加了总瘦肉组织质量（14.8%）。RAP-031使脊髓损伤后的前肢肌肉质量分别增加了二头肌和三头肌的38%和19%（p < 0.001）。RAP-031和SCI-VEH组之间后肢肌肉重量没有差异。在腓肠肌中，与假手术组相比，SCI-VEH中白细胞介素（IL）-6（8倍）、IL-1 β（3倍）和肿瘤坏死因子α（8倍）的信使RNA（mRNA）表达升高。RAP-031组中肌肉RING指蛋白1 mRNA是假手术组的2倍。RAP-031不影响细胞因子表达。股骨远端和胫骨近端的骨矿物质密度在SCI后降低（分别为-26%和-28%），RAP-031没有改变。总之，MST抑制增加了病变上的肌肉质量，但不能防止病变下的肌肉或骨丢失，或瘫痪肌肉中的炎症。
Myostatin (MST) is a potent regulator of muscle growth and size. Spinal cord injury (SCI) results in marked atrophy of muscle below the level of injury. Currently, there is no effective pharmaceutical treatment available to prevent sublesional muscle atrophy post-SCI. To determine whether inhibition of MST with a soluble activin IIB receptor (RAP-031) prevents sublesional SCI-induced muscle atrophy, mice were randomly assigned to the following groups: Sham-SCI; SCI+Vehicle group (SCI-VEH); and SCI+RAP-031 (SCI-RAP-031). SCI was induced by complete transection at thoracic level 10. Animals were euthanized at 56 days post-surgery. RAP-031 reduced, but did not prevent, body weight loss post-SCI. RAP-031 increased total lean tissue mass compared to SCI-VEH (14.8%). RAP-031 increased forelimb muscle mass post-SCI by 38% and 19% for biceps and triceps, respectively (p < 0.001). There were no differences in hindlimb muscle weights between the RAP-031 and SCI-VEH groups. In the gastrocnemius, messenger RNA (mRNA) expression was elevated for interleukin (IL)-6 (8-fold), IL-1 beta (3-fold), and tumor necrosis factor alpha (8-fold) in the SCI-VEH, compared to the Sham group. Muscle RING finger protein 1 mRNA was 2-fold greater in the RAP-031 group, compared to Sham-SCI. RAP-031 did not influence cytokine expression. Bone mineral density of the distal femur and proximal tibia were decreased post-SCI (-26% and -28%, respectively) and were not altered by RAP-031. In conclusion, MST inhibition increased supralesional muscle mass, but did not prevent sublesional muscle or bone loss, or the inflammation in paralyzed muscle.