School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China; Chongqing Research Institute, Harbin Institute of Technology, Chongqing 401135, China; National and Local Joint Engineering Laboratory for Synthesis, Transformation and Separation of Extreme Environmental Nutrients, Harbin Institute of Technology, Harbin 150001, China.
Chongqing Research Institute, Harbin Institute of Technology, Chongqing 401135, China; National and Local Joint Engineering Laboratory for Synthesis, Transformation and Separation of Extreme Environmental Nutrients, Harbin Institute of Technology, Harbin 150001, China; School of Medicine and Health, Harbin Institute of Technology, Harbin 150001, China.
Int J Biol Macromol. 2024 Oct;278(Pt 1):134432. doi: 10.1016/j.ijbiomac.2024.134432. Epub 2024 Aug 7.
In this study, a combination of adenine and potassium oxonate was utilized to establish a hyperuricemic nephropathy (HN) mouse model, aiming to elucidate the effect through which Imperata Cylindrica polysaccharide (ICPC-a) ameliorates HN. In HN mice, an elevation in the abundance of Erysipelatoclostridium, Enterococcus, Prevotella, and Escherichia-Shigella was observed, whereas Lactobacillus and Bifidobacterium declined. Additionally, the systemic reductions in the levels of acetate, propionate, and butyrate, along with a significant increase in indole content, were noted. HN mice demonstrated intestinal barrier impairment, as evidenced by diminished mRNA expression of ZO-1, Occludin, and Claudin-1 and increased Mmp-9 levels. The pro-inflammatory factors IL-6, IL-17, TNF-α, IFN-γ, and COX-2 were overexpressed. Subsequent gavage intervention with ICPC-a markedly mitigated the inflammatory response and ameliorated colon tissue damage. ICPC-a effectively regulated the abundance of gut microbiota and their metabolites, including short-chain fatty acids (SCFAs), bile acids (BAs), and indole, promoting the correction of metabolic and gut microbiota imbalances in HN mice. These findings underscored the capacity of ICPC-a as a prebiotic to modulate gut microbiota and microbial metabolites, thereby exerting a multi-pathway and multi-targeted therapeutic effect on HN.
在这项研究中，我们使用腺嘌呤和氧嗪酸钾联合建立了高尿酸血症肾病（HN）小鼠模型，旨在阐明贯叶金丝桃多糖（ICPC-a）改善 HN 的作用机制。在 HN 小鼠中，观察到肠杆菌属、粪肠球菌属、普雷沃氏菌属和大肠埃希氏-志贺氏菌属丰度增加，而乳杆菌属和双歧杆菌属减少。此外，还观察到系统中乙酸盐、丙酸盐和丁酸盐的水平降低，吲哚含量显著增加。HN 小鼠表现出肠道屏障损伤，ZO-1、Occludin 和 Claudin-1 的 mRNA 表达减少，Mmp-9 水平升高。促炎因子 IL-6、IL-17、TNF-α、IFN-γ和 COX-2 表达过度。随后用 ICPC-a 灌胃干预可显著减轻炎症反应并改善结肠组织损伤。ICPC-a 可有效调节肠道微生物群及其代谢物的丰度，包括短链脂肪酸（SCFAs）、胆汁酸（BAs）和吲哚，促进 HN 小鼠代谢和肠道微生物群失衡的纠正。这些发现强调了 ICPC-a 作为一种益生元的能力，可调节肠道微生物群及其代谢物，从而对 HN 发挥多途径、多靶点的治疗作用。
