Li Xue-Ying, Wang Yu-Jing, Chen Shun, Pan Li-Hua, Li Qiang-Ming, Luo Jian-Ping, Zha Xue-Qiang
Engineering Research Centre of Bioprocess of Ministry of Education, Hefei University of Technology, No 193 Tunxi Road, Hefei 230009, People's Republic of China.
School of Food and Biological Engineering, Hefei University of Technology, No 193 Tunxi Road, Hefei 230009, People's Republic of China.
J Agric Food Chem. 2022 Mar 30;70(12):3633-3643. doi: 10.1021/acs.jafc.1c07483. Epub 2022 Feb 15.
The present work aimed to explore the effect and underlying mechanism of a homogeneous polysaccharide (LJP61A) on macrophage polarization in high-fat-diet-fed LDLr mice and Ox-LDL-induced macrophages. Results showed that LJP61A remarkably reduced the lesion burden in atherosclerotic mice, alleviated lipid deposition in Ox-LDL-stimulated macrophages, decreased the expression of M1 macrophage markers, and increased the expression of M2 macrophage markers, thus reducing the M1/M2 macrophage phenotype ratio. Meanwhile, the autophagic flux of macrophages was enhanced by LJP61A treatment and . 3-Methyladenine is an autophagic inhibitor. As expected, this inhibitor blocked the effects of LJP61A on macrophage polarization. SIRT1 and FoxO1 are two key upstream genes that control the autophagy behavior. We also found that LJP61A significantly up-regulated the expression of SIRT1 and FoxO1. However, these effects of LJP61A were abolished by the SIRT1 siRNA and FoxO1 inhibitor AS1842856. These results suggested that LJP61A reduced atherosclerosis in HFD-induced LDLr mice via regulating autophagy-mediated macrophage polarization.
本研究旨在探讨一种均质多糖（LJP61A）对高脂饮食喂养的低密度脂蛋白受体（LDLr）小鼠和氧化型低密度脂蛋白（Ox-LDL）诱导的巨噬细胞中巨噬细胞极化的影响及其潜在机制。结果显示，LJP61A显著减轻了动脉粥样硬化小鼠的病变负担，减轻了Ox-LDL刺激的巨噬细胞中的脂质沉积，降低了M1巨噬细胞标志物的表达，并增加了M2巨噬细胞标志物的表达，从而降低了M1/M2巨噬细胞表型比率。同时，LJP61A处理增强了巨噬细胞的自噬通量。3-甲基腺嘌呤是一种自噬抑制剂。正如预期的那样，这种抑制剂阻断了LJP61A对巨噬细胞极化的影响。沉默信息调节因子1（SIRT1）和叉头框蛋白O（FoxO1）是控制自噬行为的两个关键上游基因。我们还发现，LJP61A显著上调了SIRT1和FoxO1的表达。然而，LJP61A的这些作用被SIRT1小干扰RNA（siRNA）和FoxO1抑制剂AS1842856消除。这些结果表明，LJP61A通过调节自噬介导的巨噬细胞极化减轻了高脂饮食诱导的LDLr小鼠的动脉粥样硬化。
