线粒体乙醛脱氢酶2对β淀粉样蛋白所致神经元损伤的作用及机制

摘要

Objective To investigate the role of mitochondrial aldehyde dehydrogenase 2 ( ALDH2) on neuronal damage induced byβ-amyloid( Aβ) .Methods HT-22 mouse hippocampal neuronal cell line was used, MTT was used to determine Aβconcentration.Western bolt was used to detect ALDH2 protein level, ELISA was used to detect 4-HNE content, luciferase enzyme was used to detect intracellular ATP content.Results The cell survival rate was significantly decreased when HT22 cells loaded with 50 μmol/L Aβ25~35 .The expression level of ALDH2 protein and the cell survival rate of HT22 did not change when intervened by ALDH2 activator Alda-1 and the inhibitor Daid-zin, further experimental results showed that Alad-1 could improve the increased 4-HNE content and the reduced ATP in HT22 when cells loaded Aβ25~35 .Conclusions ALDH2 activation might elicit neuronal protective effect against Aβ25~35 through reducing 4-HNE levels and increasing ATP content of the intracellular.%目的：探讨线粒体乙醛脱氢酶（ALDH）2对β淀粉样蛋白（Aβ）所致神经元损伤的作用及机制。方法应用HT－22小鼠海马神经元细胞系，MTT法检测明确Aβ25～35负载浓度制成Aβ神经元损伤模型；ALDH2激活剂Alda－1、ALDH2抑制剂Daidzin 干预后，Western印迹检测ALDH2蛋白表达水平；并采用ELISA检测4－HNE含量、以荧光素酶法检测细胞内的ATP含量。结果 HT22细胞负载Aβ25～35（浓度50μmol／L）时细胞生存率有显著降低；ALDH2激活剂Alda－1、ALDH2抑制剂 Daidzin 干预后，ALDH2蛋白表达水平并未发生变化，也并未导致细胞生存率改变；加入 Alad－1后负载Aβ25～35的HT22细胞4－HNE含量显著减少，细胞内ATP含量明显提高，与Aβ组相比较有显著差异（P＜0．05）。结论 ALDH2激活后能有效减轻Aβ导致的神经元损伤，可能通过减少细胞内4－HNE含量、增加ATP含量实现其细胞保护的作用。