Department of Microbiology and Immunology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan.
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan.
Int J Mol Sci. 2024 Jul 18;25(14):7847. doi: 10.3390/ijms25147847.
This study investigated the effects of cilostazol on motor dysfunction, spinal motor neuron abnormalities, and schwannopathy in rats with diabetes. Diabetes mellitus (DM) was induced in rats via femoral intravenous streptozotocin (STZ) injection (60 mg/kg). After successful DM induction, cilostazol was administered on day 15 via oral gavage (100 mg/kg/day) for 6 weeks until sacrifice. Behavioral assays, including motor function, were performed weekly. The sciatic nerve, L5 spinal cord, and spinal ventral root were collected to evaluate the expression of the glial fibrillary acidic protein (GFAP), myelin protein zero (P0), and choline acetyltransferase (ChAT) by immunofluorescence and Western blotting. DM rats displayed decreased running speeds, running distances, and toe spread but increased foot pressure. In addition, loss of non-myelinating Schwann cells and myelin sheaths was observed in the sciatic nerve and L5 spinal ventral root. Reduced numbers of motor neurons were also found in the L5 spinal ventral horn. Cilostazol administration significantly potentiated running speed and distance; increased hind paw toe spread; and decreased foot pressure. In the sciatic nerve and L5 spinal ventral root, cilostazol treatment significantly improved non-myelinated Schwann cells and increased myelin mass. ChAT expression in motor neurons in the spinal ventral horn was improved, but not significantly. Cilostazol administration may protect sensorimotor function in diabetic rats.
本研究旨在探讨西洛他唑对糖尿病大鼠运动功能障碍、脊髓运动神经元异常和雪旺病的影响。通过股静脉注射链脲佐菌素（STZ）（60mg/kg）诱导大鼠糖尿病。成功诱导糖尿病后，于第 15 天开始通过口服灌胃（100mg/kg/天）给予西洛他唑 6 周，直至处死。每周进行行为学评估，包括运动功能。收集坐骨神经、L5 脊髓和脊髓腹根，通过免疫荧光和 Western blot 评估神经胶质纤维酸性蛋白（GFAP）、髓鞘蛋白零（P0）和胆碱乙酰转移酶（ChAT）的表达。糖尿病大鼠表现出运动速度、运动距离和足趾张开度降低，但足底压力增加。此外，坐骨神经和 L5 脊髓腹根中非髓鞘雪旺细胞和髓鞘丢失。L5 脊髓腹角的运动神经元数量也减少。西洛他唑给药显著提高了运动速度和距离，增加了后足趾张开度，并降低了足底压力。在坐骨神经和 L5 脊髓腹根中，西洛他唑治疗显著改善了非髓鞘雪旺细胞并增加了髓鞘质量。脊髓腹角运动神经元中的 ChAT 表达得到改善，但不显著。西洛他唑给药可能对糖尿病大鼠的感觉运动功能具有保护作用。
