A combination of prostaglandin E1 analogue and aldose reductase inhibitor normalizes the reduction in sciatic nerve conduction velocity in chronically streptozocin-diabetic rats.
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Considering the implication of vascular and metabolic disruption in the pathogenesis and progression of diabetic neuropathy (DN), we investigated the effects of a combination of prostaglandin (PG) E<SUB>1</SUB> analogue, OP 1206·α CD (OP), and aldose reductase inhibitor (ARI), ICI 128436 (ICI), on the polyneuropathy in long-term streptozocin (STZ)-induced diabetic (DM) rats. DM rats were treated daily with OP alone (10μg/kg/day), OP (10μg/kg/day) and ICI (35mg/kg/day), or saline by gastric gavage for 2months, heginning 5 months after induction of diabetes. Age-matched non-DM rats were treated with saline in the same manner, as controls.<BR>Body weight reduction and hyperglycemia of DM rats were unchanged throughout the experiment irrespective of treatment. The reduction in sciatic motor nerve conduction velocity in DM rats (49.8±2.1m/s), p<0.01 vs control (57.6±1.4) was significantly improved at the end of the experiment with OP (53.2±1.7, p<0.05 vs untreated DM), and was normalized by treatment with the combination of OP and ICI (55.9±1.7, p<0.01 vs untreated DM). Sciatic sorbitol accumulation and myo-inositol depletion in DM rats were improved only by the combined regimen. Impaired sciatic Na+, K+-ATPase activity in DM rats, moreover, was restored to the control level with this regimen.<BR>These results suggest that (1) a combination of PGEi and ARI may be more effectivefor neuropathy in long-term STZ-DM rats, (2) both vascular and metabolic disruptions may be implicated in the progression of DN, and (3) this combination therapy should be considered for the treatment of human DN.
- 一般社団法人 日本糖尿病学会の論文
一般社団法人 日本糖尿病学会 | 論文
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