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依达拉奉右莰醇通过抑制氧化应激和提高自噬流促进周围神经损伤修复

Edaravone Dexborneol facilitates peripheral nerve regeneration through suppressing oxidative damage and autophagy flow
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摘要 目的:探讨依达拉奉右莰醇(C-EDA)对氧化应激以及自噬流的调控在周围神经损伤(PNI)中的作用。方法:PNI模型的建立和分组:将大鼠按照随机数字表法分为Sham组、PNI组、C-EDA组(C-EDA+PNI)、3MA(3-甲基腺嘌呤)组(PNI+C-EDA+3MA),每组10只。术后第4周对所有大鼠进行步态印记检测,神经电生理检测,腓肠肌湿重测量,肌肉组织HE染色,神经组织NF-200+MBP免疫荧光染色。用Western blot法检测体内的氧化应激相关蛋白Nrf2、HO-1,自噬相关蛋白LC3II/LC3I、p62,凋亡相关蛋白Bcl-2、Bax的表达情况。结果:与PNI组相比,C-EDA+PNI改善后足畸形,改善神经传导功能以及减轻腓肠肌萎缩。与PNI组相比,CEDA治疗上调体内的氧化应激相关蛋白Nrf2、HO-1、抗凋亡蛋白Bcl-2的表达,下调自噬底物蛋白p62、促凋亡蛋白Bax的表达(P<0.05)。3MA逆转了C-EDA改善损伤后的神经功能的效应。结论:C-EDA能够通畅自噬流,从而发挥改善PNI后神经结构修复与功能恢复的作用,是治疗PNI的一种潜在有效的方法。 Objective:To investigate the role of Edaravone Dexborneol(C-EDA)in regulating oxidative stress and autophagy flow in peripheral nerve injury(PNI).Methods:PNI model was established by moderate crush injury to the sciatic nerve with a vascular clamp.The rats were randomly divided into Sham group,PNI group,C-EDA group(C-EDA+PNI),and 3MA group[PNI+C-EDA+3MA(3-methyladenine)].At the 4th week after operation,gait imprinting,neuroelectrophysiological detection,wet weight measurement of gastnemius muscle,HE staining of muscle tissue and NF-200+MBP immunofluorescence staining of nerve tissue were performed in all rats.The levels of oxidative stress-related proteins Nrf2 and HO-1,autophagy related proteins LC3 II/LC3 I and p62(autophagy substrate protein,reflecting whether autophagy flow was unobstructed),apoptosisrelated proteins Bcl-2 and Bax were detected by Western blot.Results:Compared with the PNI group,C-EDA+PNI improved the posterior foot deformity,improved nerve conduction function and reduced gastrecnemius atrophy.3MA reversed the effect of C-EDA on improving neurological function after injury.Compared with PNI group,C-EDA up-regulated the expressions of oxidative stress-related proteins Nrf2,HO-1 and anti-apoptotic protein Bcl-2,and down-regulated the expressions of autophagy substrate protein p62 and pro-apoptotic protein Bax(P<0.05).Conclusion:Our study confirms that C-EDA can unobstruct autophagy flow,playing a role in improving neural structure repair and functional recovery after PNI.Therefore,it is a potentially effective method for the treatment of PNI.
作者 谌靖豪 楼承浩 魏圣哲 卢颖枫 余方正 王健 CHEN Jinghao;LOU Chenghao;WEI Shengzhe;LU Yingfeng;YU Fangzheng;WANG Jian(Department of Wound Repair,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015,China;Department of Hand Surgery and Peripheral Neurosurgery,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015,China;School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou 325035,China)
出处 《温州医科大学学报》 CAS 2023年第7期517-525,共9页 Journal of Wenzhou Medical University
基金 国家自然科学基金项目(8217051594)。
关键词 周围神经损伤 依达拉奉右莰醇 氧化应激 自噬流 神经功能 peripheral nerve injury Edaravon Dexborneol oxidative stress autophagy flow neural function
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