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基于转录组学探讨广叶绣球菌多糖对小鼠肝脏糖代谢紊乱的调控机制

杨二晨¹, 贾丰荧², 张莉敏², 靳丽阳², 任道勤², 姜悦², 云少君², 冯翠萍^2,*

¹山西农业大学体育部，晋中 030801；²山西农业大学食品科学与工程学院，晋中 030801

摘要

本研究旨在探讨广叶绣球菌多糖(Sparassis latifolia polysaccharides, SLPs)对高脂饮食联合链脲佐菌素(streptozotocin,STZ, 40 mg/kg)诱导的小鼠肝脏糖代谢紊乱的作用及其机制。构建肝脏糖代谢紊乱小鼠模型，分别给予不同剂量SLPs (100、200、400 mg/kg)灌胃干预8 周，并设置空白对照组、模型组及阳性对照组(盐酸二甲双胍)。通过丙酮酸耐量试验(pyruvatetolerance test, PTT)、肝糖原含量测定、肝脏组织形态学观察(HE 染色和油红O 染色)、转录组学分析，以及RT-qPCR 和Western blot 验证关键信号通路，系统评估SLPs 的干预效果及其分子机制。结果显示，与模型组相比，中、高剂量SLPs 显著降低PTT曲线下面积，提高肝糖原含量，并改善肝脏组织病理损伤和脂质蓄积。转录组学分析显示，SLPs 干预可显著调节与糖脂代谢相关的差异表达基因，这些基因富集于磷脂酰肌醇3-激酶(phosphatidylinositol-3-kinase, PI3K)/蛋白激酶B(protein kinase B, AKT)/叉头框蛋白O1 (forkhead box O1, FOXO1)等信号通路。进一步验证发现，SLPs 可上调糖代谢紊乱小鼠肝脏胰岛素样生长因子1 受体(insulin-like growth factor 1 receptor, IGF1R)、蛋白激酶B2 (protein kinase B2, AKT2)、磷脂酰肌醇3-激酶调节亚基1 (phosphatidylinositol-3-kinase regulatory subunit 1, PIK3R1) mRNA表达水平，下调FOXO1 和果糖-1,6-二磷酸酶1 (fructose-1,6-bisphosphatase 1, FBP1) mRNA表达水平；同时，SLPs 可上调糖代谢紊乱小鼠肝脏p-FOXO1 蛋白表达水平，下调磷酸烯醇式丙酮酸羧激酶(phosphoenolpyruvate carboxykinase, PEPCK)蛋白表达水平。以上结果提示，SLPs 可激活PI3K/AKT/FOXO1 信号通路，从而改善高脂饮食联合STZ所致的小鼠肝脏糖代谢紊乱，其机制涉及抑制糖异生关键酶活性和促进葡萄糖利用。

关键词： 广叶绣球菌多糖; 糖代谢; 肝脏; 转录组学; PI3K/AKT/FOXO1信号通路

Exploring the regulatory mechanism of Sparassis latifolia polysaccharides on hepatic glucose metabolism disorders in mice based on transcriptomics

YANG Er-Chen¹, JIA Feng-Ying², ZHANG Li-Min², JIN Li-Yang², REN Dao-Qin², JIANG Yue², YUN Shao-Jun², FENG Cui-Ping^2,*

¹Department of Physical Education, Shanxi Agricultural University, Jinzhong 030801, China；²College of Food Science and Engineering, Shanxi Agricultural University, Jinzhong 030801, China

Abstract

This study aimed to investigate the effects and mechanism of Sparassis latifolia polysaccharides (SLPs) on hepatic glucose metabolism disorders induced by a high-fat diet combined with streptozotocin (STZ) in mice. A mouse model of hepatic glucose metabolism disorder was established and treated with different doses of SLPs (100, 200, and 400 mg/kg) via gavage for 8 weeks, alongside control, model, and positive control groups (metformin hydrochloride). The effects of SLPs were systematically evaluated through pyruvate tolerance tests (PTT), hepatic glycogen content measurement, liver histomorphological analysis (HE and oil red O staining), transcriptomics, and validation of key signaling pathways using RT-qPCR and Western blot. The results showed that, compared to the model group, medium and high doses of SLPs significantly reduced area under the curve (AUC) of PTT, increased hepatic glycogen content, and ameliorated liver histopathological damage and lipid accumulation in the liver. Transcriptomic analysis revealed that SLPs intervention significantly modulated differentially expressed genes related to glucose and lipid metabolism, which were enriched in signaling pathways such as phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/forkhead box O1 (FOXO1) signaling pathway. Further validation demonstrated that SLPs up-regulated mRNA expression levels of insulin-like growth factor 1 receptor (IGF1R), protein kinase B2 (AKT2), and phosphatidylinositol-3-kinase regulatory subunit 1 (PIK3R1) in the liver of mice with glucose metabolism disorders, and down-regulated the mRNA expression levels of FOXO1 and fructose-1,6-bisphosphatase 1 (FBP1). Additionally, SLPs up-regulated p-FOXO1 protein expression level and down-regulated phosphoenolpyruvate carboxykinase (PEPCK) protein expression level. These results suggest that SLPs can effectively improve hepatic glucose metabolism disorders in mice induced by a high-fat diet combined with STZ by activating the PI3K/AKT/FOXO1 signaling pathway, involving the inhibition of key gluconeogenic enzymes and promotion of glucose utilization.

Key words: Sparassis latifolia polysaccharides; glucose metabolism; liver; transcriptomics; PI3K/AKT/FOXO1 signaling pathway

收稿日期：　　录用日期：

通讯作者：冯翠萍　　E-mail:

DOI: 10.13294/j.aps.2026.0058

引用本文：

杨二晨, 贾丰荧, 张莉敏, 靳丽阳, 任道勤, 姜悦, 云少君, 冯翠萍. 基于转录组学探讨广叶绣球菌多糖对小鼠肝脏糖代谢紊乱的调控机制[J]. 生理学报 2026; 78 (3): 653-664.

YANG Er-Chen, JIA Feng-Ying, ZHANG Li-Min, JIN Li-Yang, REN Dao-Qin, JIANG Yue, YUN Shao-Jun, FENG Cui-Ping. Exploring the regulatory mechanism of Sparassis latifolia polysaccharides on hepatic glucose metabolism disorders in mice based on transcriptomics. Acta Physiol Sin 2026; 78 (3): 653-664 (in Chinese with English abstract).