Di Gregorio F, Favaro G, Fiori M G
Department of Peripheral Nervous System Research, Fidia Research Laboratories, Abano Terme, Italy.
Muscle Nerve. 1989 Dec;12(12):1017-23. doi: 10.1002/mus.880121210.
Vincristine sulfate (VCR) was administered intravenously to rats at doses of 0.25, 0.5, and 0.75 mg/kg. During the first week following VCR treatment, extensor digitorum longus (EDL) muscle contraction strength and fiber electrophysiologic parameters were measured. At all doses tested, VCR strongly reduced twitch and tetanic tension. EDL fiber resting membrane potential was affected in a dose-dependent manner, and membrane depolarization was associated with the loss of excitability. Local membrane hyperpolarization by intracellular current application restored the capacity to produce action potential (AP). However, to elicit APs with a normal rate of rise, polarizing current had to be maintained for 3-5 minutes, indicating that the removal of Na+ channel inactivation followed a slow kinetics. Minor alterations in spontaneous synaptic transmission and in evoked transmission during high-frequency repetitive stimulation were seen only at the highest dose. It is suggested that VCR impairs skeletal muscle function by affecting primarily the contractile apparatus, whereas sarcolemmal alterations are evident at increased doses of the drug.
将硫酸长春新碱（VCR）以0.25、0.5和0.75mg/kg的剂量静脉注射给大鼠。在VCR治疗后的第一周，测量趾长伸肌（EDL）的肌肉收缩强度和纤维电生理参数。在所有测试剂量下，VCR均显著降低了抽搐和强直张力。EDL纤维静息膜电位受到剂量依赖性影响，膜去极化与兴奋性丧失相关。通过施加细胞内电流使局部膜超极化可恢复产生动作电位（AP）的能力。然而，为了以正常的上升速率引发动作电位，极化电流必须维持3至5分钟，这表明钠通道失活的解除遵循缓慢的动力学过程。仅在最高剂量时观察到自发突触传递和高频重复刺激期间诱发传递的轻微改变。提示VCR主要通过影响收缩装置损害骨骼肌功能，而在药物剂量增加时肌膜改变明显。
