乙醛脱氢酶2在高糖诱导神经元损伤中的作用  

The role of ALDH2 in neuronal injury induced by high glucose

作　　者：王潇亮 熊剑 WANG Xiaoliang;XIONG Jian(Department of Neurosurgery,General Hospital of Northern Theater Command of Chinese People’s Liberation Army,Shenyang,Liaoning 110016,China)

机构地区：[1]北部战区总医院神经外科,辽宁沈阳110016

出　　处：《中华神经外科疾病研究杂志》2024年第2期7-12,共6页Chinese Journal of Neurosurgical Disease Research

摘　　要：目的 论证乙醛脱氢酶2(ALDH2)在高糖诱导神经元损伤中的作用.方法 采用体外高糖培养的HT-22神经元细胞模型,利用ALDH2的激动剂Alda-1,探索ALDH2对体外高糖培养神经元的作用.首先探索了ALDH2在不同浓度和不同处理时间的表达规律,然后利用Alda-1处理高糖培养的HT-22神经元细胞,通过TUNEL、Hoechst-PI染色、检测LDH表达评价神经元损伤情况.最后检测ROS、MDA、SOD、GSH-Px、IL-1β和IL-18,评价氧化应激和神经炎症情况.结果 高糖可以抑制ALDH2表达,且呈浓度和时间依赖性.上调ALDH2可抑制神经元凋亡,Alda-1可以减少Hoechst+/PI+细胞数量及程序性坏死标志物RIP和MLKL的表达(P<0.05).Alda-1可以抑制神经元氧化应激和神经炎症.结论 ALDH2可通过抑制程序性死亡、氧化应激和神经炎症发挥神经元保护作用.Objective To test the role of ALDH2 in diabetic encephalopathy.Methods HT-22 neuron model cultured in high glucose in vitro and Alda-1,an agonist of ALDH2,were utilized to explore the role of ALDH2 in neurons cultured in high glucose in vitro.Firstly,the expression rule of ALDH2 at different concentrations and processing times was explored.Secondly,Alda-1 was used to treat HT-22 neuronal cells cultured with high glucose,and neuronal injury was also evaluated by TUNEL,Hoechst-PI staining,and detection of LDH expression.Finally,ROS,MDA,SOD,GSH-Px,IL-1β,and IL-18 were detected to evaluate the oxidative stress and neuroinflammation.Results As high glucose could suppress the expression of ALDH2 in a manner dependent on both concentration and time,Alda-1 was employed to treat HT-22 cells cultured in high glucose.Through TUNEL staining and LDH detecting,Alda-1 could be found to inhibit apoptosis.Hoechst PI staining showed that Alda-1 could reduce Hoechst+/PI+cells,while RT-qPCR indicated that Alda-1 could downregulate the expression level of RIP and MLKL(markers of necroptosis).Ultimately,detection of ROS,MDA,SOD,GSH-Px,IL-1βand IL-18 manifested that Alda-1 could inhibit neuronal oxidative stress and neuroinflammation.Conclusion ALDH2 could suppress programmed death,oxidative stress and neuroinflammation to protect neurons away from high glucose.

关 键 词：乙醛脱氢酶2 糖尿病脑病 神经元损伤 

分 类 号：R739.41[医药卫生—肿瘤]