Hagisawa Kohsuke, Ayaori Makoto, Ikewaki Katsunori, Nakajima Motowo, Morimoto Yuji
Department of Physiology, National Defense Medical College Tokorozawa Japan.
Division of Cardiology, Tokorozawa Heart Center Tokorozawa Japan.
Circ Rep. 2019 Dec 12;2(1):60-68. doi: 10.1253/circrep.CR-19-0089.
Recently, 5-aminolevulinic acid (ALA) has been reported to modulate inflammatory development via an antioxidant effect. Hence, the aim of this study was to determine the anti-atherosclerotic effect of ALA. Low-density lipoprotein (LDL) receptor knockout mice were fed the following diets for 24 weeks: normal diet (n=6); 1.25% cholesterol diet (high-cholesterol diet, HCD; n=7); HCD+ALA (46 mg/kg/day; n=10); and HCD+ezetimibe (5 mg/kg/day; n=10). At 40 weeks, HCD+ALA had reduced LDL cholesterol (320±68 vs. 379±49 mg/dL), triglyceride (141±44 vs. 195±49 mg/dL) and oxidized LDL (380±40 vs. 422±64 pg/mL) compared with HCD only. En face lesion area for the entire aortic surface was significantly smaller in mice that received HCD+ALA than in mice that received only HCD (32±5% vs. 39±4%, P<0.05). ALA intake exogenously increased tissue heme oxygenase-1 (HO-1) level in plaque composite tissue of the carotid arterial wall compared with HCD only (18±8 vs. 12±3 pg/μL, P<0.05), and HO-1-positive plaque showed modest NADPH oxidase 4 expression. ALA intake induces exogenous production of HO-1 at plaque sites, and improves lipid profiles and attenuation of atherosclerotic plaque progression in vivo.
最近，有报道称5-氨基乙酰丙酸（ALA）可通过抗氧化作用调节炎症发展。因此，本研究的目的是确定ALA的抗动脉粥样硬化作用。给低密度脂蛋白（LDL）受体敲除小鼠喂食以下饮食24周：正常饮食（n = 6）；1.25%胆固醇饮食（高胆固醇饮食，HCD；n = 7）；HCD + ALA（46毫克/千克/天；n = 10）；以及HCD +依泽替米贝（5毫克/千克/天；n = 10）。在40周时，与仅喂食HCD相比，HCD + ALA组的LDL胆固醇（320±68 vs. 379±49毫克/分升）、甘油三酯（141±44 vs. 195±49毫克/分升）和氧化LDL（380±40 vs. 422±64皮克/毫升）有所降低。接受HCD + ALA的小鼠整个主动脉表面的正面病变面积明显小于仅接受HCD的小鼠（32±5% vs. 39±4%，P<0.05）。与仅喂食HCD相比，外源性摄入ALA可使颈动脉壁斑块复合组织中的组织血红素加氧酶-1（HO-1）水平升高（18±8 vs. 12±3皮克/微升，P<0.05），且HO-1阳性斑块显示适度的NADPH氧化酶4表达。外源性摄入ALA可在斑块部位诱导HO-1的产生，并改善体内脂质谱和减缓动脉粥样硬化斑块进展。
