Epalrestat protects against diabetic peripheral neuropathy by alleviating oxidative stress and inhibiting polyol pathway  

作　　者：Qing-rong Li Zhuo Wang Wei Zhou Shou-rui Fan Run Ma Li Xue Lu Yang Ya-shan Li Hong-li Tan Qi, ng-hua Shao Hong-ying Yang 

机构地区：[1]Second Affiliated Hospital of Kunming Medical University, Department of Clinical Laboratory, Kunming, Yunnan Province, China [2]Third People's Hospital of Yunnan Province, Kunming, Yunnan Province, China

出　　处：《Neural Regeneration Research》2016年第2期345-351,共7页中国神经再生研究（英文版）

基　　金：supported by a grant from the National Natural Science Foundation of China,No.81060141

摘　　要：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.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.

关 键 词：nerve regeneration peripheral nerve injury STREPTOZOTOCIN reactive oxygen species diabetic neuropathy oxidative stress aldosereductase antioxidant enzymes polyol pathway aldose reductase inhibitor superoxide dismutase CATALASE glutathione peroxidase rats NSFCgrant neural regeneration 

分 类 号：R587.2[医药卫生—内分泌]