关键词: Abdominal aortic aneurysm Apoptosis Glutamine MMP ROS

Mesh : Animals Aortic Aneurysm, Abdominal / pathology prevention & control metabolism Apoptosis / drug effects Mice Glutamine / pharmacology Angiotensin II / pharmacology Macrophage Activation / drug effects Muscle, Smooth, Vascular / drug effects pathology cytology Humans Myocytes, Smooth Muscle / drug effects metabolism Oxidative Stress / drug effects Reactive Oxygen Species / metabolism Disease Models, Animal Male Macrophages / drug effects metabolism immunology Aorta, Abdominal / pathology drug effects Matrix Metalloproteinase 9 / metabolism Matrix Metalloproteinase 2 / metabolism Tumor Necrosis Factor-alpha / metabolism Interleukin-6 / metabolism Calcium Phosphates

来  源:   DOI:10.7150/ijms.96395   PDF(Pubmed)

Abstract:
Glutamine (Gln), known as the most abundant free amino acid, is widely spread in human body. In this study, we demonstrated the protective effects of glutamine against mouse abdominal aortic aneurysm (AAA) induced by both angiotensin II (AngII) and calcium phosphate (Ca3(PO4)2) in vivo, which was characterized with lower incidence of mouse AAA. Moreover, histomorphological staining visually presented more intact elastic fiber and less collagen deposition in abdominal aortas of mice treated by glutamine. Further, we found glutamine inhibited the excessive production of reactive oxide species (ROS), activity of matrix metalloproteinase (MMP), M1 macrophage activation, and apoptosis of vascular smooth muscle cells (VSMCs) in suprarenal abdominal aortas of mice, what\'s more, the high expressions of MMP-2 protein, MMP-9 protein, pro-apoptotic proteins, and IL-6 as well as TNF-α in protein and mRNA levels in cells treated by AngII were down-regulated by glutamine. Collectively, these results revealed that glutamine protected against mouse AAA through inhibiting apoptosis of VSMCs, M1 macrophage activation, oxidative stress, and extracellular matrix degradation.
摘要:
谷氨酰胺(Gln),被称为最丰富的游离氨基酸,在人体中广泛传播。在这项研究中,我们证明了谷氨酰胺对血管紧张素II(AngII)和磷酸钙(Ca3(PO4)2)在体内诱导的小鼠腹主动脉瘤(AAA)的保护作用,其特征是小鼠AAA的发病率较低。此外,组织形态学染色在接受谷氨酰胺处理的小鼠的腹主动脉中可见更完整的弹性纤维和更少的胶原蛋白沉积。Further,我们发现谷氨酰胺抑制了活性氧化物(ROS)的过量产生,基质金属蛋白酶(MMP)活性,M1巨噬细胞活化,小鼠肾上腹主动脉血管平滑肌细胞(VSMC)凋亡,更重要的是,MMP-2蛋白高表达,MMP-9蛋白,促凋亡蛋白,经AngII处理的细胞中的蛋白质和mRNA水平中的IL-6以及TNF-α被谷氨酰胺下调。总的来说,这些结果表明,谷氨酰胺通过抑制VSMCs的凋亡来保护小鼠AAA,M1巨噬细胞活化,氧化应激,和细胞外基质降解。
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