Kikkawa R, Hatanaka I, Yasuda H, Kobayashi N, Shigeta Y
Metabolism. 1984 Mar;33(3):212-4. doi: 10.1016/0026-0495(84)90038-6.
A potent inhibitor of aldose reductase, (E)-3-carboxy-methyl-5-[(2E)-methyl-3-phenylpropenylidene]rhodanin e (ONO-2235), was orally administered at a dose of 20 mg X kg-1 X d-1 for 2 weeks to streptozotocin-diabetic rats from the beginning of the diabetic state, ie, 24 hours after streptozotocin injection. The impairment of motor nerve conduction velocity (MNCV) of the tail nerve found in nontreated diabetic rats was apparently prevented by the treatment with the aldose reductase inhibitor (24.5 +/- 0.4 v 29.0 +/- 1.4 m/s on day 14, P less than 0.005). Those diabetic rats treated with the compound actually showed an age-dependent increase in MNCV similar to that of normal control rats (25.5 +/- 1.5 v 26.4 +/- 1.0 m/s on day 7, 29.0 +/- 1.4 v 29.4 +/- 1.3 m/s on day 14, treated v normal, not statistically significant on both days). The sorbitol content of the sciatic nerve excised from ONO-2235-treated diabetic rats (0.067 +/- 0.018 nmol/g wet weight) was significantly lower than that of the nontreated diabetic rats (1.309 +/- 0.080 nmol/g wet weight, P less than 0.001) but significantly higher than that of normal control rats (0.229 +/- 0.015 nmol/g wet weight, P less than 0.001). These results suggest that the reduction in MNCV noted in the experimental diabetic animals is not the result of retarded maturation of peripheral nerves but of metabolic derangement caused by the diabetic state, which can be prevented by suppressing sorbitol accumulation in nerve tissue. It also appears that there may be a threshold level of sorbitol accumulation that causes the impairment of nerve conduction velocity.
从糖尿病状态开始（即链脲佐菌素注射后24小时）起，给链脲佐菌素诱导的糖尿病大鼠口服一种强效醛糖还原酶抑制剂，（E）-3-羧甲基-5-[(2E)-甲基-3-苯基亚丙烯基]罗丹宁（ONO-2235），剂量为20mg·kg⁻¹·d⁻¹，持续2周。未治疗的糖尿病大鼠中发现的尾神经运动神经传导速度（MNCV）损伤，通过醛糖还原酶抑制剂治疗得到明显预防（第14天，24.5±0.4对29.0±1.4m/s，P＜0.005）。用该化合物治疗的那些糖尿病大鼠实际上显示出MNCV随年龄增长，类似于正常对照大鼠（第7天，25.5±1.5对26.4±1.0m/s，第14天，29.0±1.4对29.4±1.3m/s，治疗组对正常组，两天均无统计学意义）。从接受ONO-2235治疗的糖尿病大鼠切除的坐骨神经山梨醇含量（0.067±0.018nmol/g湿重）显著低于未治疗的糖尿病大鼠（1.309±0.080nmol/g湿重，P＜0.001），但显著高于正常对照大鼠（0.229±0.015nmol/g湿重，P＜0.001）。这些结果表明，实验性糖尿病动物中观察到的MNCV降低不是周围神经成熟延迟的结果，而是糖尿病状态引起的代谢紊乱的结果，这可以通过抑制神经组织中山梨醇积累来预防。似乎也可能存在一个导致神经传导速度受损的山梨醇积累阈值水平。
