Fahim M A, el-Sabban F, Davidson N
Department of Physiology, Faculty of Medicine, U.A.E. University, United Arab Emirates.
Anat Rec. 1998 Jun;251(2):240-4. doi: 10.1002/(SICI)1097-0185(199806)251:2<240::AID-AR13>3.0.CO;2-O.
Peripheral neuropathy of both motor and sensory nerves has been well documented in diabetes mellitus, but the evidence for physiological and correlated morphological changes during the pathogenesis of myopathy is scarce. In the present report, we have chosen the dorsiflexor muscle of adult male mice as a model for studying in situ muscle contraction and neuromuscular ultrastructure during the pathogenesis of streptozotocin-induced diabetes.
Thirty mice (30 g bodyweight) were injected once i.p. with streptozotocin solution (200 mg/Kg) to induce experimental diabetes mellitus. Comparative analyses of in situ muscle isometric contractile characteristics were studied (at 1 Hz, 5 Hz and 30 Hz nerve stimulation) in urethane-anesthetized (2 mg/g, i.p.) control and diabetic mice at three time points, 2 weeks, 4 weeks, and 8 weeks postinjection. Synaptic delay was also recorded in diabetic and age-matched control mice.
There was a significant increase in synaptic delay in both 4-week and 8-week diabetic mice compared with control mice (8.9 +/- 1.2 msec and 7.6 +/- 0.6 msec, respectively, compared with 6.1 +/- 0.5 msec). At all three stimulation frequencies, diabetes did not affect muscle contractile speed but significantly reduced the twitch tension after 8 weeks, with no changes at 2 weeks or 4 weeks. The recorded single-twitch tension values were 2.6 +/- 0.3 g, 2.1 +/- 0.6 g, 2.2 +/- 0.7 g, and 1.2 +/- 0.1 g for control, 2 weeks, 4 weeks, and 8 weeks, respectively. At 30 Hz, the recorded tension values were 4.6 +/- 1.6 g, 3.1 +/- 1.2 g, 3.1 +/- 1.1 g, and 2.1 +/- 1.0 g for control, 2 weeks, 4 weeks, and 8 weeks, respectively. Ultrastructural changes in neuromuscular junctions were similar to those that have been described in disuse and aging. These changes were observed after 8 weeks and included serve loss of synaptic vesicles, electron-dense bodies, and myelin-like figures as well as degeneration of mitochondria.
The results reveal that streptozotocin-induced diabetes affects presynaptically the neuromuscular junction as well as muscle itself. Actions at both sites may contribute to the functional alterations seen in muscle contractile properties and may play a role in the pathogenesis of diabetic neuromyopathy.
糖尿病患者运动和感觉神经的周围神经病变已有充分记载，但关于肌病发病机制中生理及相关形态学变化的证据却很少。在本报告中，我们选择成年雄性小鼠的背屈肌作为模型，以研究链脲佐菌素诱导的糖尿病发病机制中原位肌肉收缩及神经肌肉超微结构。
30只小鼠（体重30克）腹腔注射一次链脲佐菌素溶液（200毫克/千克）以诱导实验性糖尿病。在注射后2周、4周和8周这三个时间点，对氨基甲酸乙酯麻醉（腹腔注射，2毫克/克）的对照小鼠和糖尿病小鼠的原位肌肉等长收缩特性进行比较分析（在1赫兹、5赫兹和30赫兹神经刺激下）。还记录了糖尿病小鼠和年龄匹配的对照小鼠的突触延迟。
与对照小鼠相比，4周和8周糖尿病小鼠的突触延迟均显著增加（分别为8.9±1.2毫秒和7.6±0.6毫秒，而对照小鼠为6.1±0.5毫秒）。在所有三个刺激频率下，糖尿病不影响肌肉收缩速度，但8周后显著降低了单收缩张力，2周和4周时无变化。对照、2周、4周和8周时记录的单收缩张力值分别为2.6±0.3克、2.1±0.6克、2.2±0.7克和1.2±0.1克。在30赫兹时，对照、2周、4周和8周时记录的张力值分别为4.6±1.6克、3.1±1.2克、3.1±1.1克和2.1±1.0克。神经肌肉接头的超微结构变化与废用和衰老中所描述的相似。这些变化在8周后观察到，包括突触小泡严重丢失、电子致密体、髓鞘样结构以及线粒体变性。
结果显示链脲佐菌素诱导的糖尿病对神经肌肉接头以及肌肉本身的突触前部位有影响。这两个部位的作用可能导致肌肉收缩特性的功能改变，并可能在糖尿病性神经肌病的发病机制中起作用。
