Role of nitric oxide in muscle regeneration following eccentric muscle contractions in rat skeletal muscle
Role of nitric oxide in muscle regeneration following eccentric muscle contractions in rat skeletal muscle
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DOI：
10.1007/s12576-013-0262-y
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发表时间：
2013-07-01
影响因子：
2.3
通讯作者：
Best, Thomas M.
中科院分区：
文献类型：
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作者：
Sakurai, Tomonobu;Kashimura, Osamu;Best, Thomas M.
我们研究了一氧化氮（NO）在重复偏心收缩（ECC）后肌肉修复和再生中的作用。采用标准化的运动方案，采用特制的等速试验装置和40次ECCs，在电刺激下对48只雄性Wistar大鼠（体重250-350 g）左胫骨前肌造成偏心收缩性损伤。一半动物（N = 24）的日粮中加入一氧化氮合酶抑制剂N(G)-硝基- l -精氨酸甲酯(L-NAME; 35 mg kg(-1) day(-1))，从ECC前3天开始持续到整个实验期间，而另一半动物（N = 24）则采用对照日粮。ECC/+ L-NAME和ECC/-L-NAME在ECC协议后0,1,3和7天被杀死（每天n = 6）。在每个时间点，未运动和未运动的对侧肢体分别作为对照肌。评估肌肉NO含量、骨骼肌损伤、白细胞浸润、钙蛋白酶活性、MyoD和myogenin表达。NO具有促炎和抗炎特性，并且NO在骨骼肌损伤中的几种可能作用已被假设。ECC/-L-NAME组各时间点NO含量均高于ECC/+ L-NAME组（p < 0.05）。此外，ECC/+ L-NAME与ECC/-L-NAME在第0天和第3天NO含量均有显著差异（p < 0.05）。在ECC发作后1天，ECC/-L-NAME组一氧化氮水平升高。ECC 3天后，与ECC/+ L-NAME组相比，ECC/-L-NAME组肌纤维损伤（通过β -葡糖苷酶活性测量）和白细胞侵袭更大。ECC 1 d后，ECC/-L-NAME肌calpain活性显著高于对照组（p < 0.05）。第3天和第7天，两组的Myo-D和myogenin基因表达均升高；然而，ECC/+ l - name处理的动物的再生程度较低。这些数据表明，一氧化氮动力学在骨骼肌损伤偏心肌收缩后再生过程中各种因素的调节中具有重要意义。
We examined the role of nitric oxide (NO) in muscle repair and regeneration following repetitive eccentric contractions (ECC). A standardized exercise protocol was used to create eccentric contraction-induced injury to the left tibialis anterior muscle of 48 male Wistar rats (body wt 250-350 g), using a customized isokinetic test device and a bout of 40 ECCs under electrical stimulation. A nitric oxide synthase inhibitor, N(G)-nitro-L-arginine-methyl ester (L-NAME; 35 mg kg(-1) day(-1)), was included in the diet for half the animals (n = 24) beginning 3 days prior to the ECC and continuing throughout the experiment, whereas the other half (n = 24) received a control diet. ECC/+ L-NAME and ECC/-L-NAME were killed after the ECC protocol at 0, 1, 3 and 7 days (n = 6 on each day). An unexercised contralateral limb with and without L-NAME infusion served as a respective control muscle at each time point. Muscle NO content, skeletal muscle damage, leukocyte infiltration, calpain activity, and MyoD and myogenin expression were assessed. NO has both pro-inflammatory and anti-inflammatory properties, and several possible roles for NO in skeletal muscle damage have been postulated. NO content was greater in the ECC/-L-NAME group at all time points (p < 0.05) compared to ECC/+ L-NAME. Additionally, significant differences in NO content were observed on day 0 (p < 0.05), and day 3 (p < 0.05), ECC/+ L-NAME versus ECC/-L-NAME. One day following the bout of ECC, and NO levels were increased in the ECC/-L-NAME group. Three days following ECC, there was greater myofiber damage (measured by beta-glucuronidase activity) and leukocyte invasion in the ECC/-L-NAME group as compared to the ECC/+ L-NAME group. One day after ECC, calpain activity was significantly increased in ECC/-L-NAME compared with control muscles (p < 0.05). On days 3 and 7, Myo-D and myogenin gene expression was increased in both groups; however, the degree of regeneration was less in the ECC/+ L-NAME-treated animals. These data suggest that NO dynamics have important implications in the regulation of various factors during skeletal muscle regeneration following damaging eccentric muscle contractions.