摘要目的 探讨可溶性环氧化物水解酶抑制剂(sEHi)对急性冠脉综合征(ACS)患者外周血单个核细胞脂肪酸合酶(FASN)表达的影响.方法 入选ACS患者35例为ACS组,体检健康者30名为对照组.于入院后24h内分别测定血脂谱、空腹血糖、心肌酶谱和超敏C反应蛋白(hs-CRP).同时分离培养外周血单个核细胞,以不同浓度可溶性环氧化物水解酶抑制剂(t-AUCB)干预,用实时荧光定量PCR、蛋白印迹法分别测定FASN及IL-6的mRNA及蛋白表达水平.结果 (1)ACS组血清hs-CRP浓度为(5.6±4.1)mg/L,与对照组(1.3±0.9 )mg/L比较显著升高,差异有统计学意义(P＜0.05)；与对照组比较,ACS组单个核细胞内FASN、IL-6 mRNA及蛋白的表达水平均显著升高(相对表达量:FASN mRNA:1比1.709±0.272,FASN蛋白:0.407±0.065比1.298±0.087;IL-6mRNA:1比2.302±0.200,IL-6蛋白:0.715±0.058比1.146±0.083,P＜0.05),且FASN、IL-6 mRNA表达量分别与血清hs-CRP浓度呈正相关(r=0.714,P＜0.01；r=0.685,P＜0.01).(2) t-AUCB可呈剂量依赖性抑制ACS组单个核细胞的FASN和IL-6 mRNA与蛋白表达,t-AUCB干预组与空白对照组(t-AUCB)比较,差异均有统计学意义(均P＜0.05)(其中t-AUCB 0、10、50、100 μmol/L组中,FASNmRNA相对表达量分别为:1,0.813±0.038,0.564±0.100,0.293±0.043;FASN分别为:0.957±0.280,0.935±0.275,0.855±0.253,0.685±0.206.结论 ACS患者体内有较高的炎症水平,其外周血单个核细胞中FASN的表达水平与体内炎症反应密切相关,t-AUCB抑制单个核细胞内的FASN表达及炎症反应,可能起到稳定斑块的作用.

abstractsObjective To explore the effects of soluble epoxide hydrolase inhibitor (sEHi) on the expressions of fatty acid synthase (FASN) mRNA and protein in peripheral blood mononuclear cell (PBMCs) of patients with acute coronary syndrome (ACS) and to discuss the influences of sEHi in the regulated expression of FASN and inflammatory reaction.Methods The hospitalized ACS patients were selected as the ACS group (n =35 ) while the healthy normal subjects as the control group (n =30).The levels of lipoproteins,fasting blood glucose,myocardial enzyme and hs-CRP (high-sensitive C-reactive protein) were measured within 24 hours after admission.Meanwhile the PBMCs were separated and cultured and then t-AUCB was added in various concentrations (0,1,10,50,100 μmol/L). The cellular expressions of FASN,IL-6 mRNA and protein were detected by real-time PCR (polymerase chain reaction)and Western blot respectively.Results ( 1 )The serum concentration of hs-CRP reached (5.6 ± 4.1 )mg/L in the ACS group.And it was obviously higher than ( 1.3 ± 0.9 ) mg/L in the control group ( P ＜ 0.05 ).Compared with the control group,the expression levels of FASN,IL-6 mRNA and protein significantly increased in the ACS group ( the relative expression amount of FASN mRNA: 1 vs 1.709 ± 0.272,FASN protein: 0.407 ± 0.065 vs 1.298 ± 0.087 ; relative expression amount of IL-6 mRNA: 1 vs 2.302 ± 0.200,IL-6 protein: 0.715 ± 0.058 vs 1.146 ± 0.083,P ＜ 0.05 ).Moreover,the levels of FASN and IL-6 mRNA had positive correlations with the serum concentration of hs-CRP ( r =0.714,P ＜ 0.01 ; r =0.685,P ＜0.01).(2) Compared with the control group (t-AUCB 0 μmol/L),10,50,100 μmol/L t-AUCB had inhibited the expressions quantity of FASN,IL,-6 mRNA and protein in PBMCs from the ACS group (P ＜ 0.05 ).The relative expressions of FASN mRNA in t-AUCB 0,10,50,100 μmol/L group were 1,0.813 ± 0.038,0.564 ±0.100,0.293 ±0.043 respectively.The relative expressions of FASN protein in t-AUCB 0,10,50 and 100 μmol/L group were 0.957 ± 0.280,0.935 ± 0.275,0.855 ± 0.253,0.685 ± 0.206respectively.Conclusion The inflammatory level increases obviously in the ACS group.And the expression level of FASN in PBMCs is closely correlated with the inflammatory level in the ACS patients; t-AUCB may prevent the ruptures of atherosclerotic lesions by regulating FASN and inhibiting inflammatory reactions in ACS patients.