Oishi Y, Yamamoto H, Nagano M, Miyamoto E, Futatsuka M
Department of Physical Education, Faculty of General Education, Kumamoto University, Japan.
Toxicol Appl Pharmacol. 1996 Jul;139(1):15-21. doi: 10.1006/taap.1996.0138.
We examined the effects of 2,5-hexanedione (2,5-HD) and acrylamide (ACR) on the muscle fiber types and myosin heavy chain (MHC) isoform composition of the slow-twitch soleus and fast-twitch plantaris muscles of rats. We employed two differently designed experiments with respect to the dosage levels and treatment periods for developing clinical neuropathies. When male Wistar rats were subcutaneously injected with 4.5 mmol of 2,5-HD/kg or 0.4 mmol of ACR/kg, 5 days a week, they developed paralysis of the hindlimbs in 4 weeks (high-dosage experiment). When they were subcutaneously injected with 3.5 mmol of 2,5-HD/kg or 0.35 mmol of ACR/kg, 5 days a week, paralysis of the hindlimbs did not develop until 6 weeks (low-dosage experiment). We examined mainly the rats treated with the neurotoxicants for 4 and 8 weeks in the high-and low-dosage experiments, respectively. Significant decreases in the maximum motor conduction velocity of the sciatic nerves were observed in the hindlimbs of the rats in both experiments. The weights of the soleus and plantaris muscles were significantly reduced in the 2,5-HD-treated rats in both experiments, while in the ACR-treated rats, the weights of both muscles decreased only in the low-dosage experiment. We could not detect any changes in the fiber type composition of the muscles by any of the treatments. However, biochemical analysis revealed decreases in the values (percentage) of the relative amounts of fast-type MHC IIa and IIb isoforms to total MHC isoforms in the 2,5-HD-treated rats, but not in the ACR-treated rats in the high-dosage experiment. In contrast, significant differences in the relative amounts of MHC isoforms were not observed after administration of the low dosage of 2,5-HD. These results suggest that 2,5-HD preferentially disorders the muscle fibers which contain the MHC II isoform. These effects may occur only after the relatively acute intoxication of 2,5-HD at a high dosage.
我们研究了2,5 -己二酮（2,5 - HD）和丙烯酰胺（ACR）对大鼠慢肌比目鱼肌和快肌跖肌的肌纤维类型及肌球蛋白重链（MHC）亚型组成的影响。针对引发临床神经病变的剂量水平和治疗周期，我们采用了两种不同设计的实验。当雄性Wistar大鼠每周5天皮下注射4.5 mmol/kg的2,5 - HD或0.4 mmol/kg的ACR时，4周后出现后肢麻痹（高剂量实验）。当它们每周5天皮下注射3.5 mmol/kg的2,5 - HD或0.35 mmol/kg的ACR时，直到6周后才出现后肢麻痹（低剂量实验）。在高剂量和低剂量实验中，我们分别主要检查了用神经毒物处理4周和8周的大鼠。在两个实验中，均观察到大鼠后肢坐骨神经的最大运动传导速度显著降低。在两个实验中，2,5 - HD处理的大鼠比目鱼肌和跖肌的重量均显著减轻，而在ACR处理的大鼠中，仅在低剂量实验中两块肌肉的重量有所下降。通过任何一种处理，我们均未检测到肌肉纤维类型组成的变化。然而，生化分析显示，在高剂量实验中，2,5 - HD处理的大鼠中，快速型MHC IIa和IIb亚型相对于总MHC亚型的相对含量（百分比）值降低，而ACR处理的大鼠未出现这种情况。相比之下，低剂量2,5 - HD给药后，未观察到MHC亚型相对含量的显著差异。这些结果表明，2,5 - HD优先扰乱含有MHC II亚型的肌纤维。这些影响可能仅在2,5 - HD高剂量相对急性中毒后才会出现。
