Preventive effect of long-term aldose reductase inhibition (ponalrestat) on nerve conduction and sural nerve structure in the spontaneously diabetic Bio-Breeding rat.
Preventive effect of long-term aldose reductase inhibition (ponalrestat) on nerve conduction and sural nerve structure in the spontaneously diabetic Bio-Breeding rat.
复制标题
长期醛糖还原酶抑制（ponalrestat）对自发性糖尿病生物育种大鼠神经传导和腓肠神经结构的预防作用。
DOI：
10.1172/jci114585
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Greene,DA
中科院分区：
文献类型：
--
作者：
Sima,AA;Prashar,A;Zhang,WX;Chakrabarti,S;Greene,DA
为验证抑制醛糖还原酶可预防或延缓胰岛素缺乏性糖尿病大鼠(BB-鼠)功能性和结构性神经病变的发生发展的假说，在糖尿病发病后即刻开始给高血糖大鼠服用醛糖还原酶抑制剂(ARI)25 mg/kg体重，并持续4~6个月。Ponalrest治疗4mo后，完全阻止了兰维尔结节特有的神经传导减慢和结构异常，尽管仅部分保留了轴突的完整性。Ponalrest治疗6个月后，神经传导减慢、轴突连接异常和轴突退行性改变得到部分但显著的预防。这种不完全但显着的预防神经病变的方法表明，除多元醇途径激活外，其他机制可能在糖尿病神经病变的发病机制中起重要作用。或者，本研究中使用的剂量可能不足以实现完全预防。尽管ARI治疗对高血糖BB大鼠的变性周围神经改变只有部分保护作用，但治疗6个月后再生神经纤维增加了三倍多。这些数据表明，预防性ARI治疗可能在延缓糖尿病神经病变的发展方面有效。
To test the hypothesis that aldose reductase inhibition may prevent or delay the development of functional and structural neuropathy in the insulin-deficient diabetic Bio-Breeding rat (BB-rat), hyperglycemic rats were begun on the aldose reductase inhibitor (ARI) ponalrestat 25 mg/kg body wt soon after the onset of diabetes and followed for 4 or 6 mo. Ponalrestat treatment completely prevented the characteristic nerve conduction slowing and structural abnormalities of the node of Ranvier for 4 mo despite only partial preservation of axonal integrity. Ponalrestat treatment for 6 mo achieved a partial but significant prevention of nerve conduction slowing, axoglial dysjunction, and axonal degenerative changes. This incomplete but significant prevention of neuropathy by ponalrestat suggests that additional mechanisms besides polyol-pathway activation may be of importance in the pathogenesis of diabetic neuropathy. Alternatively, the dosage used in the present study may not have been sufficient to achieve a complete prevention. Despite the only partial protective effect of ARI treatment on degenerative peripheral nerve changes in hyperglycemic BB-rats, 6 mo of treatment resulted in a more than threefold increase in regenerating nerve fibers. These data suggest that prophylactic ARI treatment may be efficacious in delaying the development of diabetic neuropathy.Images