REINNERVATION AND RECOVERY OF MOUSE SOLEUS MUSCLE AFTER LONG-TERM DENERVATION
REINNERVATION AND RECOVERY OF MOUSE SOLEUS MUSCLE AFTER LONG-TERM DENERVATION
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DOI：
10.1016/0306-4522(90)90236-w
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发表时间：
1990-01-01
期刊：
影响因子：
3.3
通讯作者：
WERNIG, A
中科院分区：
文献类型：
--
作者：
IRINTCHEV, A;DRAGUHN, A;WERNIG, A
在约7个月的去神经期后2-10个月研究小鼠比目鱼肌的再神经支配和恢复情况。为维持右侧坐骨神经的去神经支配，每隔2周冷冻14次。虽然最初有间歇性的肌肉再神经支配，但到第五神经冻结时，失神经支配肌肉的收缩力降至对侧肌肉的10%以下，此后进一步下降。神经重建后，比目鱼肌力量恢复缓慢，5-6个月后达到平台值。术后5 ~ 10个月对侧肌肉强直肌力平均达到72% (58 ~ 86%,n = 12) （P < 0.01，绝对值t检验），术后10个月对侧肌肉强直肌力平均达到87% （P < 0.05,n = 5）。在再神经支配的肌肉中肌纤维直径明显减小，但在再神经支配肌肉和对照肌肉中频率分布正常且形状相似，表明在再神经支配2个月后肌肉神经完全再支配，无去神经支配纤维。再神经组肌纤维总数相似（842±73sd）。，n = 15)，对侧（854±104sd）。，n = 15)和对照比目鱼肌（853±77S.D）。，n = 5)。最后一次冷冻后3个月再生比目鱼神经有髓轴突数量达到对照组，6个月继续增加（为对照组的150%），此后下降（9-10个月为对照组的125%）。在对侧比目鱼神经中，有髓鞘轴突的数量在此期间保持不变。神经纤维直径仍然异常小；即使在10个月后，神经纤维直径仍呈单峰分布，平均直径为3.3μm，而完整神经的纤维直径为双峰分布（平均值分别为3.9 μm和9.0μm）。每根神经的总纤维横截面积随着时间的增加而增加，但仅达到54%±6sd。， （n = 3）对侧神经10个月。9-10个月后髓鞘相对厚度（g-ratio）恢复正常。解剖上，肌肉神经重建在7-8周完成，因为没有异常小的肌纤维剖面。然而，功能上，神经支配未成熟，原因如下：乙酰胆碱（50mg/l高氯酸乙酰胆碱）引起的挛缩仍比正常大（17%±4sd）。，n = 6，最大破伤风力与3%±1sd相比。正常肌肉n = 12)，神经诱发性破伤风（50 Hz，持续2s）表现为疲劳，峰值仅为86%±6S.D。（n = 5）为直接肌肉刺激获得的肌力。即使在3个月时，乙酰胆碱挛缩也略有升高（8%±2 S.D,n = 6,P < 0.05），高镁低钙Tyrode组神经诱发反应的阻滞阻力（传播安全边际）降低。5-10个月后未发现神经相关参数的缺损。在7-8周时，纤维类型分布异常，因为大多数肌纤维染色为酸稳定型肌球蛋白atp酶（I型纤维，pH值为4.5），只有少数染色为碱稳定型肌球蛋白atp酶（IIB型，pH值为10.3），一些染色为两种类型（IIC型）。因此，I型纤维的频率下降，到3个月时纤维类型分布接近正常对照动物的值。令人惊讶的是，在对侧肌肉中观察到类似的盈余，然后是I型纤维的减少。在去神经支配期和再神经支配期轮式跑步对再神经支配肌（+ 17%）和对侧控制肌（+ 14%）的肌力均有适度的积极影响，而仅在再神经支配期（5-6个月）进行训练。
Reinnervation and recovery of the mouse soleus muscle were studied 2–10 months after denervation periods of about 7 months. To maintain denervation the right sciatic nerve was frozen 14 times at 2-week intervals. Though initially intermittent muscle reinnervation occurred, contractile force of denervated muscles was reduced to less than 10% of the contralateral muscles by the fifth nerve freezing and further declined thereafter.Following reinnervation, recovery of soleus muscle force proceeded slowly to reach plateau values after 5–6 months. Tetanic muscle force reached on average 72% (range 58–86%,n = 12) of contralateral muscles after 5–10 months, (P < 0.01,t-testfor absolute values) and 87% of unoperated animals after 10 months (P < 0.05,n = 5). Muscle fibre diameters were significantly reduced in reinnervated muscles, but frequency distributions were normal and similarly shaped in reinnervated and control muscles, suggesting complete muscle reinnervation and the absence of denervated fibres even at 2 months of reinnervation. Total numbers of muscle fibres were similar in reinnervated (842 ± 73S.D.,n = 15), contralateral (854 ± 104S.D.,n = 15) and control soleus muscles (853 ± 77S.D.,n = 5).The number of myelinated axons in regenerating soleus nerves reached control values by 3 months after the last freezing, continued to increase till 6 months (150% of control), and declined thereafter (125% at 9–10 months). In the contralateral soleus nerves the number of myelinated axons remained constant during this period. Nerve fibre diameters remained abnormally small; even after 10 months of reinnervation fibre diameters were unimodally distributed with a mean diameter of 3.3μm in contrast to the bimodal distribution in intact nerves (mean values 3.9 and 9.0μm, respectively). Total fibre cross-section area per nerve increased with time but reached only 54% ± 6S.D., (n = 3) of contralateral nerves by 10 months. The relative thickness of the myelin sheath (g-ratio) returned to normal after 9–10 months.Anatomically, muscle reinnervation appeared to be complete by 7–8 weeks since unusually small muscle fibre profiles were absent. Functionally, however, innervation was rendered immature for the following reasons: acetylcholine-induced contractures (50mg/l acetylcholine perchlorate) were still larger than normal (17% ± 4S.D.,n = 6, of maximum tetanic force as compared to3% ± 1S.D.in normal muscles,n = 12), nerve-evoked tetani (50 Hz for 2s) showed fatigue and peak values reached only86% ± 6S.D.(n = 5) of the muscle force obtained from direct muscle stimulation. Even by 3 months acetylcholine contractures were slightly elevated (8% ± 2 S.D.,n = 6,P < 0.05) and block resistance of the nerve-evoked responses in high magnesium/low calcium Tyrode (safety margin of transmission) was reduced. No deficits in nerve-related parameters were found after 5–10 months of reinnervation. At 7–8 weeks of reinnervation fibre type distribution was abnormal since most muscle fibres stained for acid-stable myosin ATPase (Type I fibres, pH 4.5), only a few for alkaline-stable myosin ATPase (Type IIB, pH 10.3), and some for both (Type IIC). Consequently, the frequency of Type I fibres declined and by 3 months fibre type distribution approached values in normal control animals. Surprisingly, in contralateral muscles a similar surplus followed by a decline in Type I fibres was observed. Running in wheels during the denervation and reinnervation periods had moderately positive effects on muscle force of both reinnervated (plus 17%) and contralateral control muscles (plus 14%), while training during the reinnervation period only (5–6 months …