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黄芪多糖通过抑制ROS/NLRP3和调节EMT减轻奶牛乳腺纤维化的机制

Mechanism of Astragalus Polysaccharide in Alleviating Bovine Mammary Fibrosis Through ROS/NLRP3 Inhibition and EMT Regulation.

作者信息

Zhang Jiang, Liu Kejiang, Yang Tingji, Duan Hongwei, Xiao Longfei, Zhang Quanwei, Zhang Yong, Dong Weitao, Zhao Xingxu

机构信息

College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.

Gansu Provincial Key Laboratory of Animal Reproductive Physiology and Reproductive Regulation, Lanzhou 730070, China.

出版信息

Antioxidants (Basel). 2025 Apr 23;14(5):503. doi: 10.3390/antiox14050503.

DOI:10.3390/antiox14050503
PMID:40427385
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12108477/
Abstract

Mastitis in dairy cows, typically caused by bacterial infection, is a common inflammatory condition of the mammary tissue that leads to fibrosis, adversely affecting cow health, milk production, and dairy product quality. Astragalus polysaccharide (APS) has shown effectiveness in alleviating inflammation and fibrosis in various organs. The study employed lipopolysaccharide (LPS) to induce fibrotic conditions in two experimental systems: MAC-T bovine mammary epithelial cells and Kunming mouse models. Key parameters, including relative gene mRNA expression, protein levels, and reactive oxygen species (ROS) levels, were assessed using RT-qPCR, Western blotting (WB), and 2',7'-Dichlorofluorescin diacetate (DCFH-DA) techniques, while histological analysis of mammary tissue was performed using H&E and Masson trichrome staining. Measuring malondialdehyde (MDA) levels, assessing the enzyme activities of catalase (CAT), and superoxide dismutase (SOD) were two methods of assessing oxidative stress. These methods were also tested in mouse mammary glands. APS significantly decreased ROS concentrations ( < 0.01), restored oxidative stress balance in mice ( < 0.05), and reduced fibrosis and inflammation, as demonstrated by histological observations and analysis. It also exerted regulatory effects on fibrosis markers (, , ) and inflammation markers (, , , ), as demonstrated by changes in their mRNA and protein expression. These findings endorse APS's viability as an alternative therapeutic agent for mammary fibrosis therapy by demonstrating its ability to inhibit epithelial-mesenchymal transition (EMT) in vitro and mammary fibrosis in vivo, while also mitigating ROS production and reducing inflammation.

摘要

奶牛乳腺炎通常由细菌感染引起,是乳腺组织常见的炎症性疾病,可导致纤维化,对奶牛健康、产奶量和乳制品质量产生不利影响。黄芪多糖(APS)已显示出在减轻各种器官炎症和纤维化方面的有效性。该研究采用脂多糖(LPS)在两个实验系统中诱导纤维化状态:MAC-T牛乳腺上皮细胞和昆明小鼠模型。使用RT-qPCR、蛋白质印迹法(WB)和2',7'-二氯二氢荧光素二乙酸酯(DCFH-DA)技术评估包括相对基因mRNA表达、蛋白质水平和活性氧(ROS)水平在内的关键参数,同时使用苏木精-伊红(H&E)和Masson三色染色对乳腺组织进行组织学分析。测量丙二醛(MDA)水平、评估过氧化氢酶(CAT)和超氧化物歧化酶(SOD)的酶活性是评估氧化应激的两种方法。这些方法也在小鼠乳腺中进行了测试。组织学观察和分析表明,APS显著降低了ROS浓度(<0.01),恢复了小鼠的氧化应激平衡(<0.05),并减少了纤维化和炎症。它还对纤维化标志物( 、 、 )和炎症标志物( 、 、 、 )发挥调节作用,这通过它们mRNA和蛋白质表达的变化得以证明。这些发现通过证明APS在体外抑制上皮-间质转化(EMT)和在体内抑制乳腺纤维化的能力,同时减轻ROS产生和减少炎症,证实了其作为乳腺纤维化治疗替代治疗剂的可行性。

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本文引用的文献

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Int J Mol Sci. 2025 Mar 26;26(7):3029. doi: 10.3390/ijms26073029.
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Astragalus membranaceus and its monomers treat peritoneal fibrosis and related muscle atrophy through the AR/TGF-β1 pathway.黄芪及其单体通过AR/TGF-β1通路治疗腹膜纤维化及相关肌肉萎缩。
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Activation of ARP2/3 and HSP70 Expression by Lipoteichoic Acid: Potential Bidirectional Regulation of Apoptosis in a Mastitis Inflammation Model.
脂磷壁酸激活 ARP2/3 和 HSP70 的表达:乳腺炎炎症模型中细胞凋亡的潜在双向调控。
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Ginsenoside Rg1 Alleviates Lipopolysaccharide-Induced Fibrosis of Endometrial Epithelial Cells in Dairy Cows by Inhibiting Reactive Oxygen Species-Activated NLRP3.人参皂苷Rg1通过抑制活性氧激活的NLRP3减轻脂多糖诱导的奶牛子宫内膜上皮细胞纤维化。
Animals (Basel). 2023 Dec 1;13(23):3723. doi: 10.3390/ani13233723.
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Astragalus polysaccharide promotes autophagy and alleviates diabetic nephropathy by targeting the lncRNA Gm41268/PRLR pathway.黄芪多糖通过靶向 lncRNA Gm41268/PRLR 通路促进自噬并减轻糖尿病肾病。
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