College of Life Sciences, Jilin Agricultural University, Changchun 130118, Jilin, China.
College of Life Sciences, Jilin Agricultural University, Changchun 130118, Jilin, China; Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, Jilin Agricultural University, Changchun 130118, China.
Int J Biol Macromol. 2023 Mar 1;230:123154. doi: 10.1016/j.ijbiomac.2023.123154. Epub 2023 Jan 5.
Lead (Pb) can cause damages to the brain, liver, kidney, endocrine and other systems. Flammulina velutipes residues polysaccharide (FVRP) has been reported to exhibit anti-heavy metal toxicity on yeast, but its regulating mechanism is unclear. Therefore, the protective effect and the underlying mechanism of FVRP on Pb-intoxicated mice were investigated. The results showed that FVRP could reduce liver and kidney function indexes, serum inflammatory factor levels, and increase antioxidant enzyme activity of Pb-poisoned mice. FVRP also exhibited a protective effect on histopathological damages in organs of Pb-intoxicated mice. Furthermore, FVRP attenuated Pb-induced kidney injury by inhibiting apoptosis via activating the Akt/GSK3β/Nrf-2/HO-1 signaling pathway. In addition, based on 16 s rRNA and ITS-2 sequencing data, FVRP regulated the imbalance of gut microbiota to alleviate the damage of Pb-poisoned mice by increasing the abundance of beneficial microbiota (Lachnospiraceae, Lactobacillaceae, Saccharomyces and Mycosphaerella) and decreasing the abundance of harmful microbiota (Muribaculaceae and Pleosporaceae). In conclusion, FVRP inhibited kidney injury in Pb-poisoned mice by inhibiting apoptosis via activating Akt/GSK3β/Nrf-2/HO-1 signaling pathway, and regulating gut fungi and gut bacteria. This study not only revealed the role of gut fungi in Pb-toxicity, but also laid a theoretical foundation for FVRP as a natural drug against Pb-toxicity.
铅（Pb）可损害脑、肝、肾、内分泌等系统。金针菇多糖（FVRP）已被报道对酵母具有抗重金属毒性作用，但作用机制尚不清楚。因此，本研究旨在探究 FVRP 对 Pb 中毒小鼠的保护作用及其潜在机制。结果表明，FVRP 可降低 Pb 中毒小鼠的肝肾功能指标、血清炎症因子水平，增加抗氧化酶活性，对 Pb 中毒小鼠的各组织器官的病理损伤具有保护作用。此外，FVRP 通过激活 Akt/GSK3β/Nrf-2/HO-1 信号通路抑制细胞凋亡，减轻 Pb 诱导的肾损伤。基于 16S rRNA 和 ITS-2 测序数据，FVRP 通过增加有益菌（Lachnospiraceae、Lactobacillaceae、Saccharomyces 和 Mycosphaerella）丰度和降低有害菌（Muribaculaceae 和 Pleosporaceae）丰度来调节肠道菌群失衡，缓解 Pb 中毒小鼠的损伤。总之，FVRP 通过激活 Akt/GSK3β/Nrf-2/HO-1 信号通路抑制细胞凋亡，调节肠道真菌和细菌，抑制 Pb 中毒小鼠的肾损伤。本研究不仅揭示了肠道真菌在 Pb 毒性中的作用，也为 FVRP 作为天然抗 Pb 毒性药物提供了理论基础。
