高浓度葡萄糖诱导的神经元毒性及分子机制  

High glucose-induced neurotoxicity and its mechanism

作　　者：常梦圆 孙文静 徐新军 付晓艳 CHANG Meng-yuan;SUN Wen-jing;XU Xin-jun;FU Xiao-yan(College of Basic Medicine,Shandong First Medical University&Shandong Academy of Medical Sciences,Taian 271000,China)

机构地区：[1]山东第一医科大学(山东省医学科学院)基础医学院,山东泰安271000

出　　处：《泰山医学院学报》2020年第9期651-654,共4页Journal of Taishan Medical College

基　　金：山东省大学生创新创业训练计划(S201910439051)。

摘　　要：目的探讨高浓度葡萄糖介导的神经毒性及机制。方法培养PC12细胞模拟神经元,体外构建高浓度葡萄糖损伤模型;MTT方法检测高浓度葡萄糖对PC12细胞的生长抑制;流式细胞术检测PC12细胞凋亡;JC-1探针检测线粒体膜电位的改变;Western blotting检测高浓度葡萄糖对活性Caspase-3和活性Caspase-9表达的影响。结果葡萄糖剂量依赖性地抑制了PC12细胞的生长,如600、800 mM葡萄糖处理细胞48 h抑制率分别是35.6%和47.1%(P<0.01);流式结果表明,高糖处理诱导了细胞明显凋亡,如400、600 mM葡萄糖处理分别诱导了36.3%和51.2%细胞凋亡(P<0.01);JC-1分析结果显示,葡萄糖处理导致了线粒体膜电位显著降低;Western blotting结果表明,葡萄糖处理显著上调了活性Caspase-3和活性Caspase-9的表达。结论高浓度葡萄糖可通过启动线粒体介导的细胞凋亡抑制PC12细胞生长,预示着潜在的神经毒性,提示抑制高糖介导的神经毒性可能是治疗糖尿病脑病的新策略。Objective:To explore glucose-induced neurotoxicity and the underlying mechanisms.Methods:PC12 cells were employed to build an in vitro high glucose-induced model.MTT assay,flow cytometry and JC-1 probe were used to detect cell viability,cell apoptosis and mitochondrial membrane potential(Δψm),respectively.Expressions of active Caspase-3 and Caspase-9 were examined by Western blotting.Results:Glucose treatment dose-dependently inhibited PC12 cell growth.For instance,the treatment of cells with 600 and 800mM glucose for 48h inhibited the cell viability by 35.6%and 47.1%respectively.Flow cytometry result indicated that 400 and 600mM glucose caused 36.3%and 51.2%cell apoptosis.JC-1 assay suggested that glucose treatment dose-dependently triggered the loss ofΔψm.Western blotting showed that glucose up-regulated the expression of active Caspase-3 and active Caspase-9.Conclusion:Glucose inhibites PC12 cell growth by triggering mitochondria-mediated apoptosis,indicating that inhibition of high glucose-induced neurotoxicity may be a new strategy in treating human diabetic encephalopathy.

关 键 词：高糖 细胞凋亡 神经毒性 糖尿病脑病 

分 类 号：R34[医药卫生—基础医学]