EFFECTS OF A NEW ALDOSE REDUCTASE INHIBITOR, (2S, 4S)-6-FLUORO-2',5'-DIOXOSPIRO[CHROMAN-4,4'-IMIDAZOLIDINE]-2-CARBOXAMIDE (SNK-860), ON THE SLOWING OF MOTOR-NERVE CONDUCTION-VELOCITY AND METABOLIC ABNORMALITIES IN THE PERIPHERAL-NERVE IN ACUTE STREPTOZOTOCIN-INDUCED DIABETIC RATS
EFFECTS OF A NEW ALDOSE REDUCTASE INHIBITOR, (2S, 4S)-6-FLUORO-2',5'-DIOXOSPIRO[CHROMAN-4,4'-IMIDAZOLIDINE]-2-CARBOXAMIDE (SNK-860), ON THE SLOWING OF MOTOR-NERVE CONDUCTION-VELOCITY AND METABOLIC ABNORMALITIES IN THE PERIPHERAL-NERVE IN ACUTE STREPTOZOTOCIN-INDUCED DIABETIC RATS
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DOI：
10.1016/0026-0495(92)90289-m
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发表时间：
1992-10-01
影响因子：
9.8
通讯作者：
KURONO, M
中科院分区：
文献类型：
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作者：
MIZUNO, K;KATO, N;KURONO, M
研究了一种新型醛糖还原酶抑制剂(2S,4S)-6-氟-2′，5′-二氧螺[铬-4,4′-咪唑烷]-2-羧酰胺（SNK-860）对急性链脲佐菌素（STZ）诱导的糖尿病大鼠运动神经传导速度（MNCV）的减慢和坐骨神经代谢异常的影响。STZ注射后2周，糖尿病大鼠的MNCV明显减慢。在接下来的2周内，SNK-860治疗以剂量依赖的方式改善了MNCV。1 mg/kg SNK-860与20 mg/kg山梨醇的药效相当。注射STZ后4周，糖尿病大鼠坐骨神经山梨醇水平升高，肌肌醇水平降低，Na+， K+-腺苷三磷酸酶（ATPase）活性降低。在糖尿病诱导后2周开始给予SNK-860 14天，以剂量依赖性的方式抑制这些代谢异常。SNK-860在2mg /kg的剂量下将所有这些参数恢复到正常水平。此外，MNCV与山梨糖醇水平密切相关（r=−）。95)，坐骨神经MNCV和肌醇水平之间的差异（r= 0.93）；山梨醇和肌醇在坐骨神经中的水平也密切相关（r= - 0.86）。因此，我们认为SNK-860对MNCV减缓的作用是通过使糖尿病患者坐骨神经中上述代谢异常正常化而产生的。因此，SNK-860可能有助于治疗糖尿病性神经病变。
The effects of a new aldose reductase inhibitor (ARI), (2S,4S)-6-fluoro-2′,5′-dioxospiro[chroman-4,4′-imidazolidine]-2-carboxamide (SNK-860), on the slowing of motor nerve conduction velocity (MNCV) and metabolic abnormalities in sciatic nerve were investigated in acute streptozotocin (STZ)-induced diabetic rats. MNCV in the diabetic rats was significantly slower 2 weeks after STZ injection. In the following 2 weeks, treatment with SNK-860 improved MNCV in a dose-dependent manner. The efficacy of 1 mg/kg SNK-860 was equipotent to that of 20 mg/kg sorbinil. Four weeks after STZ injection, increases in sorbitol levels, decreases inmyo-inositol levels, and reductions in Na+, K+-adenosine triphosphatase (ATPase) activity were observed in sciatic nerves of diabetic rats. Administration of SNK-860 for 14 days beginning 2 weeks after the induction of diabetes inhibited these metabolic abnormalities in a dose-dependent manner. SNK-860 restored all of these parameters to normal levels at a dose of 2 mg/kg. In addition, close correlations were observed between MNCV and sorbitol levels (r= −.95) and between MNCV andmyo-inositol levels (r= .93) in the sciatic nerve; a close correlation was also observed between sorbitol andmyo-inositol levels in the sciatic nerve (r= −.86). Therefore, it is suggested that the effect of SNK-860 on the slowing of MNCV results from normalizing the above-mentioned metabolic abnormalities in the sciatic nerve of diabetics. Thus, SNK-860 may be useful in the treatment of diabetic neuropathy.