Yoshida M, Sugiyama Y, Akaike N, Ashizawa N, Aotsuka T, Ohbayashi S, Matsuura A
Pharmacological Research Laboratory, Grelan Pharmaceutical Co. Ltd., Tokyo, Japan.
Diabetes Res Clin Pract. 1998 May;40(2):101-12. doi: 10.1016/s0168-8227(98)00032-1.
The effects of a novel potent aldose reductase inhibitor, GP-1447 [3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]-5-methylphenylace tic acid] on the sciatic nerve blood flow in streptozotocin-induced diabetic rats were examined. Blood flow was analyzed in terms of mass, i.e. the volume of blood in tissue, and of velocity, i.e. the velocity of the blood flow. In diabetic rats, a 63% decrease in blood flow due to a decrease in velocity was observed. The blood mass in the same animals fluctuated, thereby increasing its range of values. Treatment with GP-1447 at a dose of 30 mg/kg per day for 4 consecutive weeks following a 3-week period without treatment ameliorated the reduced blood flow by 51%, and was accompanied by a recovery of velocity. The increase in the range of blood mass values was reversed by treatment with GP-1447. The restoration of the range of blood mass values, but not that of the blood flow, by GP-1447 was blocked by treatment with the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine. Motor nerve conduction velocity (MCV) changes in parallel with blood flow values, while it is inversely proportionate to alterations in the range of blood mass values. It is suggested that the observed beneficial effect of GP-1447 on blood flow is involved in the restoration of decreased MCV in diabetes. It would appear that GP-1447-induced amelioration of neurovascular defects is not mediated solely by the improvement of the NO system.
研究了一种新型强效醛糖还原酶抑制剂GP - 1447[3 - [(4,5,7 - 三氟苯并噻唑 - 2 - 基)甲基]-5 - 甲基苯乙酸]对链脲佐菌素诱导的糖尿病大鼠坐骨神经血流的影响。从质量（即组织中的血液体积）和速度（即血流速度）方面分析了血流情况。在糖尿病大鼠中，观察到由于速度降低导致血流减少了63%。相同动物的血容量波动，从而增加了其数值范围。在未经治疗3周后，连续4周每天以30 mg/kg的剂量用GP - 1447治疗，可使减少的血流改善51%，并伴有速度的恢复。用GP - 1447治疗可逆转血容量值范围的增加。一氧化氮（NO）合酶抑制剂NG - 硝基 - L - 精氨酸的治疗可阻断GP - 1447对血容量值范围的恢复作用，但不能阻断对血流的恢复作用。运动神经传导速度（MCV）与血流值平行变化，而与血容量值范围的变化成反比。提示观察到的GP - 1447对血流的有益作用与糖尿病中降低的MCV的恢复有关。看来GP - 1447诱导的神经血管缺陷改善并非仅由NO系统的改善介导。
