新型口服依达拉奉通过下调caspase-3减轻糖尿病脑病大鼠皮质损伤  

Novel oral edaravone attenuates cortex damage in rats with diabetic encephalopathy by downregulating caspase-3

作　　者：张叶讯 梅佳佳 包露洁 杨丹妮 张幸霖 罗海芸 ZHANG Yexun;MEI Jiajia;BAO Lujie;YANG Danni;ZHANG Xinglin;LUO Haiyun(Department of Pharmacology,School of Basic Medicine,Kunming Medical University,Kunming 650500,China)

机构地区：[1]昆明医科大学基础医学院药理学系,昆明650500

出　　处：《神经解剖学杂志》2025年第1期32-38,共7页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(82260242);云南省科技厅-昆明医科大学联合专项重点项目(202301AY070001-018);云南省大学生创新性实验计划项目;昆明医科大学大学生创新性实验计划项目(2022JXD276)。

摘　　要：目的:探讨新型口服依达拉奉(EDA)对糖尿病脑病(DE)大鼠的影响。方法:应用网络药理学的研究方法预测口服EDA治疗DE的作用机制,获得交集靶点并初步进行体内验证。30只雄性SD大鼠,随机分成3组:正常(control)组、糖尿病脑病模型(DE)组和口服依达拉奉治疗(DE+EDA)组。DE组和DE+EDA组使用链脲佐茵素(STZ)法诱导糖尿病脑病模型,造模成功后DE+EDA组使用口服EDA灌胃,其余两组使用等剂量生理盐水灌胃。取样本血清检验相关脂质释放率,同时用Western blot检测脑组织氧化应激因子3-硝基酪氨酸(3-NT)、凋亡因子胱天蛋白酶3(caspase-3)蛋白表达水平。取样本脑组织做苏木精-伊红(HE)染色观察病理改变。结果:网络药理学分析得到27个核心靶点,基因生物过程功能注释结果显示,交集靶点主要富集于对氧化应激的反应、神经元凋亡等。血清相关脂质检测显示相较于DE组,DE+EDA组脂质代谢紊乱明显改善。DE组的3-NT、caspase-3相较于control组表达水平显著升高(P<0.05),而DE+EDA组相较于DE组表达明显降低(P<0.05)。HE染色可见DE组显示组织排列紊乱,细胞皱缩,质膜完整,细胞核固缩、碎裂和溶解。与DE组相比,DE+EDA组脑组织相对结构致密,排列整齐,细胞固缩、碎裂和溶解明显改善。结论:网络药理学和体内实验均初步证明口服EDA可减轻糖尿病脑病大鼠损伤。Objective:To investigate the effects of the novel oral edaravone(EDA)on rats with diabetic encephalopathy(DE).Methods:The network pharmacology research methodology was employed to elucidate the mechanism of action of oral EDA in the treatment of diabetes mellitus,identify intersecting targets,and conduct initial validation of these findings in vivo.Thirty male SD rats were randomly assigned to three groups:A normal control(control)group,a diabetic encephalopathy DE(DE)group,and an oral edaravone treatment(DE+EDA)group.Diabetic encephalopathy was induced in both the DE and DE+EDA groups using the streptozotocin(STZ)method.After successful modeling,the DE+EDA group received oral administration of EDA,while the other two groups were administered equal doses of saline as controls.Serum samples were examined for lipid release rate,and the protein expression levels of oxidative stress factor 3-nitrotyrosine(3-NT)and apoptotic factor cysteinyl aspartate specific proteinase-3(caspase-3)in brain tissues were detected by Western blot.Brain samples were stained with HE staining to observe the pathological changes.Histopathological changes were observed through hematoxylin-eosin(HE)staining.Results:Network pharmacological analysis yielded 27 core targets,and functional annotation of gene bioprocesses showed that the intersecting targets were mainly enriched in response to oxidative stress and neuronal apoptosis.Serum-related lipid assay showed that the DE+EDA group had significantly improved lipid metabolism disorders compared with the DE group.Additionally,expression levels of 3-NT and caspase-3 were significantly higher in the DE group when compared with controls(P<0.05);However,both markers exhibited a significant decrease within the DE+EDA treatment cohort as opposed to their counterparts in the DE group(P<0.05).HE staining showed that in DE group the cellular arrangement was disordered,the cells were shrunk with intact plasma membrane,and the nuclei were condensed showing karyopyknosis,fragmented and dissolved.Compared

关 键 词：口服依达拉奉 糖尿病脑病 氧化应激 凋亡 脂代谢紊乱 大鼠 

分 类 号：R28[医药卫生—中药学]