Cameron N E, Cotter M A, Hohman T C
Department of Biomedical Sciences, University of Aberdeen, Scotland, UK.
Diabetologia. 1996 Feb;39(2):172-82. doi: 10.1007/BF00403960.
Impaired omega-6 essential fatty acid metabolism and exaggerated polyol pathway flux contribute to the neurovascular abnormalities in streptozotocin-diabetic rats. The potential interactions between these mechanisms were examined by comparing the effects of threshold doses of aldose reductase inhibitors and evening primrose oil, alone and in combination, on neurovascular deficits. In addition, high-dose aldose reductase inhibitor and evening primrose oil treatment effects were challenged by co-treatment with the cyclo-oxygenase inhibitor, flurbiprofen, or the nitric oxide synthase inhibitor, NG-nitro-L-arginine. Eight weeks of diabetes caused an 18.9% reduction in sciatic motor conduction velocity (p < 0.001). This was only modestly ameliorated by a 0.1% dietary supplement of evening primrose oil or the aldose reductase inhibitors ZD5522 (0.25 mg.kg-1.day-1 and WAY121 509 (0.2 mg.kg-1.day-1 for the final 2 weeks. However, joint treatment with primrose oil and ZD5522 or WAY121 509 caused marked 71.5 and 82.4% corrections, respectively, of the conduction deficit. Sciatic nutritive blood flow was 43.1% reduced by diabetes (p < 0.001) and this was corrected by 67.8% with joint ZD5522 and primrose oil treatment (p < 0.001). High-dose WAY121 509 (10 mg. kg-1.day-1 and primrose oil (10% dietary supplement) prevented sciatic conduction velocity and nutritive blood flow deficits in 1-month diabetic rats (p < 0.001). However, these effects were abolished by flurbiprofen (5 mg.kg(-1).day-1 and NG-nitro-L-arginine (10 mg.kg-1.day-1) co-treatment (p < 0.001). Thus, the data provide evidence for synergistic interactions between polyol pathway/nitric oxide and essential fatty acid/cyclo-oxygenase systems in the control of neurovascular function in diabetic rats, from which a potential therapeutic advantage could be derived.
ω-6必需脂肪酸代谢受损和多元醇途径通量增加导致链脲佐菌素诱导的糖尿病大鼠出现神经血管异常。通过比较醛糖还原酶抑制剂和月见草油阈值剂量单独及联合使用对神经血管缺陷的影响，研究了这些机制之间的潜在相互作用。此外，通过与环氧化酶抑制剂氟比洛芬或一氧化氮合酶抑制剂NG-硝基-L-精氨酸共同处理，对高剂量醛糖还原酶抑制剂和月见草油的治疗效果提出质疑。糖尿病8周导致坐骨神经运动传导速度降低18.9%（p<0.001）。在最后2周，0.1%的月见草油饮食补充剂或醛糖还原酶抑制剂ZD5522（0.25mg·kg-1·天-1）和WAY121509（0.2mg·kg-1·天-1）只能适度改善这种情况。然而，月见草油与ZD5522或WAY121509联合治疗分别使传导缺陷得到了71.5%和82.4%的显著纠正。糖尿病使坐骨神经营养性血流量减少43.1%（p<0.001），而ZD5522和月见草油联合治疗可使血流量纠正67.8%（p<0.001）。高剂量WAY121509（10mg·kg-1·天-1）和月见草油（10%饮食补充剂）可预防1个月糖尿病大鼠的坐骨神经传导速度和营养性血流量缺陷（p<0.001）。然而，氟比洛芬（5mg·kg-1·天-1）和NG-硝基-L-精氨酸（10mg·kg-1·天-1）共同处理可消除这些作用（p<0.001）。因此，这些数据为多元醇途径/一氧化氮和必需脂肪酸/环氧化酶系统在控制糖尿病大鼠神经血管功能方面的协同相互作用提供了证据，从中可能获得潜在的治疗优势。
