Li Qing-Rong, Wang Zhuo, Zhou Wei, Fan Shou-Rui, Ma Run, Xue Li, Yang Lu, Li Ya-Shan, Tan Hong-Li, Shao Qing-Hua, Yang Hong-Ying
Second Affiliated Hospital of Kunming Medical University, Department of Clinical Laboratory, Kunming, Yunnan Province, China.
Third People's Hospital of Yunnan Province, Kunming, Yunnan Province, China.
Neural Regen Res. 2016 Feb;11(2):345-51. doi: 10.4103/1673-5374.177745.
Epalrestat is a noncompetitive and reversible aldose reductase inhibitor used for the treatment of diabetic neuropathy. This study assumed that epalrestat had a protective effect on diabetic peripheral nerve injury by suppressing the expression of aldose reductase in peripheral nerves of diabetes mellitus rats. The high-fat and high-carbohydrate model rats were established by intraperitoneal injection of streptozotocin. Peripheral neuropathy occurred in these rats after sustaining high blood glucose for 8 weeks. At 12 weeks after streptozotocin injection, rats were intragastrically administered epalrestat 100 mg/kg daily for 6 weeks. Transmission electron microscope revealed that the injuries to myelinated nerve fibers, non-myelinated nerve fibers and Schwann cells of rat sciatic nerves had reduced compared to rats without epalrestat administuation. Western blot assay and immunohistochemical results demonstrated that after intervention with epalrestat, the activities of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase gradually increased, but aldose reductase protein expression gradually diminished. Results confirmed that epalrestat could protect against diabetic peripheral neuropathy by relieving oxidative stress and suppressing the polyol pathway.
依帕司他是一种用于治疗糖尿病性神经病变的非竞争性可逆醛糖还原酶抑制剂。本研究假定依帕司他通过抑制糖尿病大鼠外周神经中醛糖还原酶的表达，对糖尿病性周围神经损伤具有保护作用。通过腹腔注射链脲佐菌素建立高脂高糖模型大鼠。这些大鼠在持续高血糖8周后出现周围神经病变。在注射链脲佐菌素12周后，大鼠每天灌胃给予依帕司他100 mg/kg，持续6周。透射电子显微镜显示，与未给予依帕司他的大鼠相比，大鼠坐骨神经的有髓神经纤维、无髓神经纤维和雪旺细胞的损伤有所减轻。蛋白质免疫印迹分析和免疫组化结果表明，依帕司他干预后，超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶等抗氧化酶的活性逐渐增加，但醛糖还原酶蛋白表达逐渐减少。结果证实，依帕司他可通过减轻氧化应激和抑制多元醇途径来预防糖尿病性周围神经病变。
