Yasuda H, Sonobe M, Hisanaga T, Kawabata T, Maeda K, Kikkawa R, Shigeta Y
Third Department of Medicine, Shiga University of Medical Science, Japan.
Metabolism. 1992 Jul;41(7):778-82. doi: 10.1016/0026-0495(92)90320-a.
In view of the possible implication of multifactorial mechanisms in the pathogenesis of diabetic neuropathy, the aldose reductase inhibitor (ARI), Statil, which ameliorates abnormal sorbitol or myo-inositol metabolism in diabetic nerves, and the prostaglandin E1 (PGE1) analogue, OP1206.alpha CD (OP), which improves diabetic vascular derangements, were administered simultaneously for 2 months to streptozocin (STZ)-induced diabetic rats with 5 months' duration of diabetes, and the effects on sciatic motor nerve conduction velocity (MNCV), Na(+)-K(+)-adenosine triphosphatase (ATPase) activity, and morphology of myelinated nerve fibers (MNF) were compared with the effects of a monotherapy with OP. The combination regimen ameliorated abnormal nerve sorbitol and myo-inositol levels and normalized decreased MNCV and enzyme activity. In contrast, neither sorbitol nor myo-inositol metabolism was ameliorated, and only insufficient improvement of MNCV and morphology of MNF was obtained with a monotherapy with OP. In addition, the combination therapy reversed both a decrease in the percent of large MNF and an increase in the percent of small MNF in diabetic rats, whereas a monotherapy with OP reversed only a decrease in the percent of large MNF. The results might suggest that a multiple-drug therapy with different mechanisms of action has greater effects on diabetic neuropathy than a single-drug therapy and is worthy of clinical consideration.
鉴于多因素机制可能参与糖尿病性神经病变的发病过程，对链脲佐菌素（STZ）诱导的病程达5个月的糖尿病大鼠，同时给予醛糖还原酶抑制剂（ARI）Statil（可改善糖尿病神经中异常的山梨醇或肌醇代谢）和前列腺素E1（PGE1）类似物OP1206.αCD（OP，可改善糖尿病性血管紊乱），持续给药2个月，并将其对坐骨神经运动神经传导速度（MNCV）、钠钾腺苷三磷酸酶（ATP酶）活性以及有髓神经纤维（MNF）形态的影响与OP单一疗法的效果进行比较。联合用药方案改善了神经中山梨醇和肌醇水平的异常，并使降低的MNCV和酶活性恢复正常。相比之下，OP单一疗法既未改善山梨醇代谢也未改善肌醇代谢，仅使MNCV和MNF形态得到了不充分的改善。此外，联合治疗逆转了糖尿病大鼠中大MNF百分比的降低和小MNF百分比的增加，而OP单一疗法仅逆转了大MNF百分比的降低。结果可能提示，作用机制不同的联合药物疗法对糖尿病性神经病变的疗效优于单一药物疗法，值得临床考虑。
