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

Effects and mechanism of mitochondrial aldehyde dehydrogenase 2 on neuronal damage caused by amyloid

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。

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 Aβ concentration.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 Daidzin,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.