Polygonatum sibiricum polysaccharides attenuate cadmium-induced bone damage, abnormal metabolism of bone marrow mesenchymal stem cells and disorder of gut microbiota(黄精多糖改善镉诱导的骨损伤、骨髓间充质干细胞代谢异常和肠道菌群紊乱)

Exposure to cadmium (Cd) can damage the bone microstructure and cause osteoporosis, but there is currently a lack of effective intervention strategies. In this study, a rat model of Cd exposure (drinking 50 mg/L CdCl2 aqueous solution for 8 weeks) and an in vitro model of osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) were established to explore the bone-protective effect of Polygonatum sibiricum polysaccharides (PRPs). The results showed that PRPs intervention could significantly improve the bone microstructure of Cd-exposed rats and repair the damage to the ileal villus structure. Immunohistochemical analysis revealed that PRPs intervention up-regulated the expressions of alkaline phosphatase, osteocalcin and bone morphogenetic protein-4 of osteogenic differentiation markers (P＜0.05). In vitro experiments confirmed that PRPs alleviated the Cd-induced inhibition of BMMSCs viability (P＜0.05) and promoted osteogenic differentiation (with increased ALP activity and decreased number of mineralized nodules, P＜0.05). Metabolomic analysis indicated that PRPs mainly exerted their protective effects by regulating central carbon metabolism, amino acid biosynthesis, and protein digestion and absorption pathways. Gut microbiota analysis showed that PRPs significantly increased the abundance of Lactobacillus by regulating the structure of gut microbiota. In conclusion, PRPs can attenuate Cd-induced bone damage, abnormal metabolism of BMMSCs, and gut microbiota disorders, providing a new strategy for precise nutritional intervention.(镉（cadmium, Cd）暴露可导致骨微结构损伤及骨质疏松症，但目前缺乏有效干预策略。本研究通过构建Cd暴露大鼠模型（饮用50 mg/L CdCl2水溶液8周）及骨髓间充质干细胞（bone marrow mesenchymal stem cells, BMMSCs）成骨分化体外模型，探讨黄精多糖（Polygonatum sibiricum polysaccharides, PRPs）的骨保护作用。结果显示：PRPs干预可显著改善Cd暴露大鼠骨微结构，并修复回肠绒毛结构损伤。免疫组织化学分析显示，PRPs干预可上调成骨分化标志物碱性磷酸酶、骨钙素及骨形态发生蛋白-4表达（P＜0.05）。体外实验证实，PRPs缓解Cd诱导的BMMSCs活力抑制（P＜0.05），同时促进成骨分化（ALP活性提高，矿化结节数减少，P＜0.05）。代谢组学分析表明，PRPs主要通过调控中枢碳代谢、氨基酸生物合成及蛋白质消化吸收通路来发挥保护作用。肠道菌群分析表明，PRPs通过调节肠道菌群结构，显著提升了乳杆菌属菌群的丰度。综上所述，PRPs可改善Cd诱导的骨损伤、BMMSCs代谢异常和肠道菌群紊乱，为精准营养干预提供了新策略。