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新型大豆多肽 dglycin 可减轻载脂蛋白 E 缺陷小鼠的动脉粥样硬化。

Novel soybean polypeptide dglycin alleviates atherosclerosis in apolipoprotein E-deficient mice.

机构信息

Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization of Ministry of Education, College of Animal and Veterinary Science, Southwest Minzu University, Chengdu, China.

Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Int J Biol Macromol. 2023 Nov 1;251:126347. doi: 10.1016/j.ijbiomac.2023.126347. Epub 2023 Aug 14.

Abstract

Atherosclerosis is a dominant cause of cardiovascular disease. Accumulation of low-density lipoproteins (LDL), formation of foam cells, and endothelial dysfunction within the arterial intima contribute to atherosclerotic plaque formation. Soy consumption is thought to have positive effect on the prevention of atherosclerosis. Therefore, in the present study, a novel soybean polypeptide dglycin was purified and characterized. Oral administration of 20 mg/g.d dglycin reduced 47.6 % lesion area, and 49.1 % lipid deposition in the atherosclerotic plaques in aortic roots in ApoE mice. In addition, it decreased the levels of 26.0 % plasma low-density lipoprotein, 27.2 % triglyceride, 40.1 % cholesterol, 25.1 % malondialdehyde and 24.2 % tumor necrosis factor-alpha (TNFα). In vitro experiments revealed that dglycin inhibited inflammatory cytokine secretion from aortic endothelial cells via the inhibition of NF-κB signaling. Furthermore, it inhibited reactive oxygen species generation, subsequently enhanced cell viability, and protected aortic endothelial cells from necrosis and apoptosis via mitochondrial function improvement. On the other hand, dglycin prevented the uptake of oxidized LDL by macrophages via suppressing the expression of scavenger receptor class A1, which suggested that dglycin prevented foam cell formation. Therefore, dglycin alleviated the early-stage of atherosclerosis via depressing inflammation, lipid deposition, protecting aortic endothelial cells and preventing foam cell formation.

摘要

动脉粥样硬化是心血管疾病的主要病因。低密度脂蛋白(LDL)的积累、泡沫细胞的形成和动脉内膜内皮功能障碍导致动脉粥样硬化斑块的形成。人们认为大豆的摄入对预防动脉粥样硬化有积极作用。因此,在本研究中,纯化并表征了一种新型的大豆多肽 dglycin。dglycin 的口服给药剂量为 20mg/g.d,可使 ApoE 小鼠主动脉根部粥样硬化斑块中的病变面积减少 47.6%,脂质沉积减少 49.1%。此外,它还降低了血浆中 26.0%的低密度脂蛋白、27.2%的甘油三酯、40.1%的胆固醇、25.1%的丙二醛和 24.2%的肿瘤坏死因子-α(TNFα)水平。体外实验表明,dglycin 通过抑制 NF-κB 信号通路抑制炎症细胞因子从主动脉内皮细胞中分泌。此外,它还抑制活性氧的产生,从而提高细胞活力,并通过改善线粒体功能来保护主动脉内皮细胞免受坏死和凋亡。另一方面,dglycin 通过抑制清道夫受体 A1 的表达来阻止巨噬细胞摄取氧化型 LDL,这表明 dglycin 可以防止泡沫细胞的形成。因此,dglycin 通过抑制炎症、脂质沉积、保护主动脉内皮细胞和防止泡沫细胞形成来缓解动脉粥样硬化的早期阶段。

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