目的 观察二十烷酸(EA)对神经元Aβ生成途径的影响及激活过氧化物酶体增殖剂激活受体α(PPARα)的干预作用.方法 将原代培养的大鼠皮质神经元分为3组:对照组、EA组、EA+ Wy14 643组.EHSA法检测培养液中Aβ含量,Western印迹法检测神经元β-淀粉样前体蛋白(APP)、β-分泌酶(BACE1)蛋白表达,RT-PCR法分析脂酰辅酶A氧化酶(ACOX1)mRNA表达.结果 EA组细胞APP、BACE1蛋白表达及Aβ生成增多(P ＜0.01,P＜0.05),ACOX1 mRNA表达加强(P＜0.05)；应用PPARα激活剂Wy14 643干预后,ACOX1 mRNA表达进一步加强(P＜0.05),细胞APP、BACE1蛋白表达及Aβ生成减少(P＜0.01,P＜0.05).结论 饱和脂肪酸可能通过促进Aβ生成在AD发病机制中起重要作用,激活PPARα有效降低了饱和脂肪酸所致的Aβ生成.%Objective To explore the effect of eicosanoic acid ( EA) on Aβ generation of rat cortical neurons and intervention of activated-PPARα. Methods Primary cultured neurons were divided randomly into three groups. Rats in EA group were administered with 40 μmol/L EA for 24 hours; Rats in EA + Wy group were administered with 40 μmol/L EA and 10 μmol/L Wy simultaneously for 24 hours. Rats in control group were treated with the medium containing the same amount of solvent. Ap content in supernatant was detected by ELISA. The protein levels of β-amyloid precursor protein (APP) and beta-site APP cleaving enzyme 1 (BACE1) were observed by Western blotting. The mRNA level of acyl-CoA oxidase 1 (AC0X1) was detected by reverse transcription-polymerase chain reaction (RT-PCR). Results APP and BACE1 protein levels and Ap content in EA group were significantly higher than those of control group (P <0. 05, P < 0. 01). Compared with EA group, APP and BACE1 protein levels and Ap content were significantly decreased ( P < 0. 01, P < 0. 05 ) in EA + Wy group. AC0X1 mRNA level was slightly increased in EA group and obviously increased in EA + Wy group. Conclusions Saturated fatty acids may be involved in AD pathogenesis through promoting Aβ production, and Aβ generation could be efficiently inhibited by PPARα activation.
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