REGENERATION AND REPAIR OF MYELINATED FIBERS IN SURAL-NERVE BIOPSY SPECIMENS FROM PATIENTS WITH DIABETIC NEUROPATHY TREATED WITH SORBINIL
REGENERATION AND REPAIR OF MYELINATED FIBERS IN SURAL-NERVE BIOPSY SPECIMENS FROM PATIENTS WITH DIABETIC NEUROPATHY TREATED WITH SORBINIL
复制标题
DOI：
10.1056/nejm198809013190905
复制
发表时间：
1988-09-01
影响因子：
158.5
通讯作者：
GREENE, DA
中科院分区：
文献类型：
--
作者：
SIMA, AAF;BRIL, V;GREENE, DA
有理由相信，糖尿病神经病变可能与山梨醇从葡萄糖通过醛糖还原酶途径积聚在神经组织中有关。醛糖还原酶抑制剂的短期治疗改善了糖尿病患者的神经传导，但长期治疗对糖尿病神经病变的神经病理变化的影响尚不清楚。为了确定更长时间的醛糖还原酶抑制是否能逆转伴随症状性糖尿病周围多神经病变的潜在损害，我们对研究中的醛糖还原酶抑制剂索比尼(每天250 mg)进行了一项随机、安慰剂对照的双盲试验。对16例糖尿病神经病变患者基线和1年后的腓肠神经活检标本进行了详细的形态计量学分析，并与所选电生理和临床指标进行了比较。与接受安慰剂治疗的患者相比，接受索比尼治疗的10名患者的神经山梨醇含量下降了41.87U 8.0%(P<；0.01)，再生有髓神经纤维的百分比增加了3.8倍(P<；0.001)，单位神经横截面积上的有髓神经纤维数量增加了33%(P=0.04)。他们在结旁脱髓鞘、节段性脱髓鞘和髓鞘皱缩程度方面也有定量的改善。纤维数量的增加伴随着神经功能改善的电生理学和临床证据。我们得出结论，索比尼作为一种针对高血糖的特定生化后果的代谢干预，可以改善糖尿病神经病变的神经病理损害。
There is reason to believe that diabetic neuropathy may be related to the accumulation of sorbitol in nerve tissue through an aldose reductase pathway from glucose. Short-term treatment with aldose reductase inhibitors improves nerve conduction in subjects with diabetes, but the effects of long-term treatment on the neuropathologic changes of diabetic neuropathy are unknown. To determine whether more prolonged aldose reductase inhibition reverses the underlying lesions that accompany symptomatic diabetic peripheral polyneuropathy, we performed a randomized, placebo-controlled, double-blind trial of the investigational aldose reductase inhibitor sorbinil (250 mg per day). Sural-nerve biopsy specimens obtained at base line and after one year from 16 diabetic patients with neuropathy were analyzed morphometrically in detail and compared with selected electrophysiologic and clinical indexes. In contrast to patients who received placebo, the 10 sorbinil-treated patients had a decrease of 41.8 7U 8.0 percent in nerve sorbitol content (P < 0.01) and a 3.8-fold increase in the percentage of regenerating myelinated nerve fibers (P < 0.001), reflected by a 33 percent increase in the number of myelinated fibers per unit of cross-sectional area of nerve (P = 0.04). They also had quantitative improvement in terms of the degree of paranodal demyelination, segmental demyelination, and myelin wrinkling. The increase in the number of fibers was accompanied by electrophysiologic and clinical evidence of improved nerve function. We conclude that sorbinil, as a metabolic intervention targeted against a specific biochemical consequence of hyperglycemia, can improve the neuropathologic lesions of diabetic neuropathy.