原人参三醇通过抑制NLRP3炎症小体激活改善巨噬细胞炎症  

Macrophage Inflammation Alleviation by 20(S)-Protopanaxatriol by Inhibiting NLRP3 Inflammasome Activation

作　　者：刘亚男 牛志强 李甫[4] 胡卫成 张迹 LIU Ya;nan;NIU Zhiqiang;LI Fu;HU Weicheng;ZHANG Ji(College of Food Science and Pharmacology,Xinjiang Agricultural University,Urumqi 830052,China;School of Life Sciences,Huaiyin Normal University,Huaian 223300,China;College of Medicine,Yangzhou University,Yangzhou 225109,China;Natural Products Research Center,Chengdu Institute of Biology,Chinese Academy of Sciences,Chengdu 610041,China)

机构地区：[1]新疆农业大学食品科学与药学学院,新疆乌鲁木齐830052 [2]淮阴师范学院生命科学学院,江苏淮安223300 [3]扬州大学医学院,江苏扬州225109 [4]中国科学院成都生物研究所天然产物研究中心,四川成都610041

出　　处：《现代食品科技》2025年第2期31-39,共9页Modern Food Science and Technology

基　　金：江苏省高等学校基础科学(自然科学)研究重大项目(23KJA550001)。

摘　　要：探究原人参三醇(20S-Protopanaxatriol,PPT)对脂多糖(Lipopolysaccharide,LPS)和三磷酸腺苷(Adenosine Triphosphate,ATP)双诱导激活Nod样受体蛋白3(NOD-Like Receptor Thermal Protein Domain Associated Protein 3,NLRP3)炎症小体的影响,从而发挥改善巨噬细胞炎症的作用。将RAW264.7细胞分为空白对照组、LPS组、LPS+ATP组和PPT给药组(20、40、80μmol/L)。经LPS+ATP诱导后,一氧化氮合酶(Inducible Nitric Oxide Sythase,iNOS)、环氧合酶2(Cyclooxygenase-2,COX-2)、白细胞介素1β(Interleukin-1β,IL-1β)、肿瘤坏死因子-α(Tumor Necrosis Factor-α,TNF-α)和NLRP3的mRNA水平显著提高。经PPT处理可显著下调iNOS、IL-1β和NLRP3的mRNA水平,而不影响COX-2和TNF-α的mRNA水平。同时,PPT可下调胞质中NLRP3、IL-1β和半胱天冬酶1(Cysteinyl Aspartate Specific Proteinase-1,Cleaved-caspase-1)蛋白的表达量,而不影响核内转录因子κB(Nuclear Factor Kappa-B,NF-κB)蛋白的水平。酶连免疫吸附(Enzyme-Linked Immunosorbnent Assay,ELISA)测定给药组可显著下调IL-1β的表达量,而对TNF-α表达量无显著变化。此外,细胞形态学观察结果显示PPT可显著改善RAW264.7炎症细胞形态,如伪足减少,细胞褶皱平缓,恢复圆形形态。该研究证明PPT可能通过抑制NLRP3炎症小体激活,进一步抑制炎症因子IL-1β的表达水平,从而发挥抗炎作用。为后期探究PPT如何靶向NLRP3炎症小体以及相关药物研发提供理论依据。The effects of 20(S)-protopanaxatriol(PPT)on NOD-like receptor thermal protein domain-associated protein 3(NLRP3)inflammasome activation induced by lipopolysaccharide(LPS)and adenosine triphosphate(ATP)were investigated to examine the role of PPT in alleviating macrophage inflammation.RAW264.7 cells were divided into a control group,an LPS group,an LPS+ATP group,and three PPT treatment groups(20,40,and 80μmol/L).The mRNA expression levels of inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2),Interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and NLRP3 were significantly increased after LPS+ATP treatment.PPT treatment markedly downregulated the mRNA levels of iNOS,IL-1β,and NLRP3;however,there were no significant changes in those of COX-2 and TNF-α.Additionally,the expression levels of NLRP3,IL-1β,and cysteinyl aspartate-specific proteinase-1 in the cell lysate of the PPT treatment group were lower than those in the LPS+ATP group;however,PPT had no effect on the translocation of nuclear factor kappa-B.Enzyme-linked immunosorbent assay revealed that PPT significantly reduced IL-1βexpression levels without affecting TNF-αlevels.Scanning electron microscopy observation showed that PPT notably improved the inflammatory state of RAW264.7 cells.Specifically,there was a decrease in pseudopodia formation,whereas cell folds were smoothed resulting in rounded cells.This study demonstrated that PPT exhibits immunomodulatory and anti-inflammatory effects.PPT can regulate inflammation in macrophages by inhibiting NLRP3 inflammasome activation and subsequently reducing the expression level of IL-1β.This study provides a theoretical basis for exploring the mechanism by which PPT targets the NLRP3 inflammasome and its potential impact on related drug development.

关 键 词：原人参三醇 抗炎作用 NLRP3炎症小体 RAW264.7 

分 类 号：R285[医药卫生—中药学]