Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, South Korea.
Eur J Pharmacol. 2012 Jan 15;674(2-3):217-26. doi: 10.1016/j.ejphar.2011.05.059. Epub 2011 May 30.
We investigated whether sulodexide has additional protective effects against peripheral nerve damage caused by microvascular dysfunction in a rat model of diabetes. Female Sprague-Dawley (SD) rats were divided into the following 4 groups (n=7-9/group): Normal, Normal+Sulodexide (sulodexide 10mg/kg), diabetic group, and diabetic+Sulodexide (sulodexide 10mg/kg). We assessed current perception threshold, skin blood flow, superoxide dismutase, and proteinuria in experimental rats after oral administration of sulodexide for 20 weeks. We also performed morphometric analysis of sciatic nerves and intraepidermal nerve fibers of the foot. Superoxide dismutase activity in the blood and sciatic nerve were increased significantly after sulodexide treatment in the diabetic group. Current perception threshold was reduced at 2000 Hz (633.3 ± 24.15 vs 741.2 ± 23.5 μA, P<0.05) and skin blood flow was improved (10.90 ± 0.67 vs 8.85 ± 0.49 TPU, P<0.05) in the diabetic+Sulodexide group compared with the diabetic group. The mean myelinated axon area was significantly larger (56.6 ± 2.2 vs 49.8 ± 2.7 μm(2), P<0.05) and the intraepidermal nerve fiber density was significantly less reduced (6.27 ± 0.24 vs 5.40 ± 0.25/mm, P<0.05) in the diabetic+Sulodexide group compared to the diabetic group. Our results demonstrate that sulodexide exhibits protective effects against peripheral nerve damage in a rat experimental model of diabetes. Therefore, these findings suggest that sulodexide is a potential new therapeutic agent for diabetic peripheral neuropathy.
我们研究了在糖尿病大鼠模型中，舒洛地特是否对微血管功能障碍引起的周围神经损伤有额外的保护作用。将雌性 Sprague-Dawley（SD）大鼠分为以下 4 组（每组 n=7-9）：正常组、正常+舒洛地特（舒洛地特 10mg/kg）组、糖尿病组和糖尿病+舒洛地特（舒洛地特 10mg/kg）组。我们在大鼠口服舒洛地特 20 周后评估了电流感知阈值、皮肤血流量、超氧化物歧化酶和蛋白尿。我们还对坐骨神经和足部表皮神经纤维进行了形态计量学分析。糖尿病组给予舒洛地特治疗后，血液和坐骨神经中超氧化物歧化酶活性显著升高。与糖尿病组相比，糖尿病+舒洛地特组的电流感知阈值在 2000Hz 时降低（633.3±24.15 vs 741.2±23.5μA，P<0.05），皮肤血流量改善（10.90±0.67 vs 8.85±0.49TPU，P<0.05）。有髓神经轴突平均面积显著增大（56.6±2.2 vs 49.8±2.7μm²，P<0.05），表皮神经纤维密度显著降低（6.27±0.24 vs 5.40±0.25/mm，P<0.05）。这些结果表明，舒洛地特对糖尿病大鼠实验模型的周围神经损伤具有保护作用。因此，这些发现表明舒洛地特是治疗糖尿病周围神经病变的一种有潜力的新治疗剂。
