Cotter M A, Cameron N E, Robertson S, Ewing I
Department of Biomedical Sciences, Marischal College, University of Aberdeen.
Exp Physiol. 1993 Mar;78(2):139-55. doi: 10.1113/expphysiol.1993.sp003675.
This study examined the effect of inhibition of aldose reductase, the first enzyme in the polyol pathway, on fast and slow twitch skeletal muscle morphology and function in streptozotocin-induced diabetes in rats. There was a preventative investigation with diabetes duration of 4 months, and a reversal investigation where treatment was given for 2 months following an untreated period of 2 months. For slow twitch soleus muscle, contractions were prolonged by diabetes, and this was partially prevented but not reversed by treatment. Relaxation was profoundly slowed, and both prevention and reversal ameliorated the changes. Diabetes had minimal effects on tension production for soleus. However, for fast twitch extensor digitorum longus, although there was little effect on speed-related contractile parameters, tetanic tension production was progressively reduced with diabetes duration. This effect was antagonized by treatment. Soleus fatigue resistance was markedly reduced by diabetes, but restored to normal by treatment. There was a reduction in oxidative enzyme staining (succinic dehydrogenase), and capillary-fibre ratio, both of which were ameliorated by aldose reductase inhibition. Mean soleus fibre area was reduced after 4 months of diabetes, and this was prevented but not reversed by treatment. Fibre area was also reduced in extensor digitorum longus, particularly for fast glycolytic fibres. There was a small amelioration with treatment. It is concluded that enhanced polyol pathway activity makes a contribution to diabetic myopathy, and that aldose reductase inhibitors can prevent this by actions on muscle fibres and their vascular supply.
本研究检测了多元醇途径中的首个酶——醛糖还原酶的抑制作用对链脲佐菌素诱导的糖尿病大鼠快、慢肌骨骼肌形态和功能的影响。进行了一项糖尿病病程为4个月的预防性研究，以及一项在2个月未治疗期后给予2个月治疗的逆转性研究。对于慢肌比目鱼肌，糖尿病会延长收缩时间，治疗可部分预防但不能逆转这种情况。舒张明显减慢，预防和逆转均可改善这种变化。糖尿病对比目鱼肌的张力产生影响最小。然而，对于快肌趾长伸肌，尽管对速度相关的收缩参数影响较小，但强直张力产生会随着糖尿病病程逐渐降低。治疗可对抗这种效应。糖尿病显著降低了比目鱼肌的抗疲劳能力，但治疗可使其恢复正常。氧化酶染色（琥珀酸脱氢酶）和毛细血管与肌纤维比例均降低，醛糖还原酶抑制可改善这两者。糖尿病4个月后比目鱼肌平均纤维面积减小，治疗可预防但不能逆转这种情况。趾长伸肌的纤维面积也减小，尤其是快糖酵解纤维。治疗有轻微改善。得出的结论是，多元醇途径活性增强导致糖尿病性肌病，醛糖还原酶抑制剂可通过作用于肌纤维及其血管供应来预防这种情况。
