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基于脂质组学与转录组学探究黄芪多糖改善癌症恶病质脂肪组织消耗的作用机制

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中草药 | 药理与临床 2026,57(1): 152-163

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中草药 |药理与临床 2026 , 57 (1) : 152 -163

基于脂质组学与转录组学探究黄芪多糖改善癌症恶病质脂肪组织消耗的作用机制

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晁兴亮¹, 苏小宇¹, 田智涵¹, 李梓源¹, 刘雪¹, 曲一玮², 王咏³, 马度芳^1,3

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通讯作者:

马度芳

作者简介:

晁兴亮: 晁兴亮,硕士研究生,研究方向为中医药防治恶病质的研究。E-mail:Xingliang1357@163.com

Mechanism of Astragalus polysaccharides in alleviating adipose tissue wasting in cancer cachexia based on lipidomics and transcriptomics

CHAO Xingliang, SU Xiaoyu, TIAN Zhihan, LI Ziyuan, LIU Xue, QU Yiwei, WANG Yong, MA Dufang

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doi: 10.7501/j.issn.0253-2670.2026.01.015

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摘要

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目的运用脂质组学、转录组学探讨黄芪多糖（Astragalus polysaccharides，APS）改善癌症恶病质（cancer cachexia，CC）脂肪组织消耗的作用机制。方法使用随机数字表法将50只雄性小鼠分为对照组、模型组和APS低、中、高剂量（200、400、800 mg/kg）组，每组10只。腹部sc CT-26结直肠癌细胞构建CC模型，给药组每日ig 0.2 mL APS溶液，对照组和模型组ig等体积的生理盐水，连续给药4周。采用苏木素-伊红（hematoxylin-eosin，HE）染色评价附睾脂肪细胞直径；ELISA法检测附睾脂肪组织肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-6（interleukin-6，IL-6）、环磷酸腺苷（cyclic adenosine monophosphate，cAMP）及血浆游离脂肪酸（free fatty acids，FFA）的水平。经有效性、显著性验证，选取对照组、模型组、APS高剂量组进行转录组学和脂质组学测序，筛选差异表达基因（differentially expressed genes，DEGs）和差异表达脂质（differentially expressed lipids，DELs），并进行富集分析；采用Western blotting法验证相关蛋白表达。结果高剂量APS干预后，小鼠附睾脂肪组织间炎症浸润减轻，脂肪细胞萎缩被显著逆转（P＜0.01），脂肪组织中TNF-α、IL-6、cAMP以及血浆FFA的水平显著降低（P＜0.01、0.001），表明高剂量APS抑制了脂肪细胞的炎症和脂解反应。脂质组学结果显示，高剂量APS干预回调了神经酰胺及其修饰物、三酰甘油等66个DELs的表达水平，代谢通路富集分析结果显示这些DELs主要涉及甘油磷脂代谢、鞘脂代谢通路。转录组学结果显示，磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinase，PI3K）-蛋白激酶B（protein kinase B，Akt）通路在DEGs中被重复富集，表明该通路可能是APS发挥作用的核心通路；此外，18个DEGs的表达被APS显著回调，基因相互作用网络图显示这些基因与Akt有复杂的互作关系。Western blotting结果验证了APS干预逆转了Tribbles同源蛋白3（Tribbles homologous protein 3，TRIB3）、磷酸化Akt（phosphorylated Akt，p-Akt、磷酸二酯酶3B（phosphodiesterase 3B，PDE3B）、磷酸化蛋白激酶A（phosphorylated protein kinase A，p-PKA）、磷酸化激素敏感脂肪酶（phosphorylated hormone sensitive lipase，p-HSL）、脂肪三酰甘油脂肪酶（adipose triglyceride lipase，ATGL）的表达水平（P＜0.05、0.01、0.001）。结论 APS可能通过减轻脂肪组织炎症反应、降低神经酰胺等鞘脂的合成，调控TRIB3-Akt轴，恢复胰岛素抗脂解、促成脂的信号传导，从而改善CC脂肪组织的消耗。

关键词

黄芪多糖 / 癌症恶病质 / 脂肪消耗 / 炎症反应 / 甘油磷脂代谢 / 鞘脂代谢 / TRIB3-Akt轴

Abstract

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Objective To explore the mechanism by which Astragalus polysaccharides (APS) improves the consumption of adipose tissue in cancer cachexia (CC) using lipidomics and transcriptomics. Methods A random number table was used to divide 50 male mice into control group, model group, APS low-, medium-and high-dose (200, 400, 800 mg/kg) groups, with 10 mice in each group. CC model was constructed using abdominal sc CT-26 colorectal cancer cells. The treatment group was given 0.2 mL APS solution by ig daily, while the control group and model group were given an equal volume of physiological saline by ig for four consecutive weeks. The diameter of epididymal adipocytes was evaluated using hematoxylin-eosin (HE) staining; ELISA method was used to detect the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cyclic adenosine monophosphate (cAMP) in epididymal adipose tissue and level of free fatty acids (FFA) in plasma. After effectiveness and significance verification, transcriptome and lipidomics sequencing were performed on control group, model group and APS high-dose group to screen differentially expressed genes (DEGs) and differentially expressed lipids (DELs), and enrichment analysis was performed; Western blotting was used to verify the expressions of relevant proteins. Results High-dose APS significantly alleviated inflammatory infiltration in epididymal adipose tissue and reversed adipocyte atrophy (P < 0.01), significantly reduced the levels of TNF-α, IL-6, cAMP in adipose tissue and level of FFA in plasma (P < 0.01, 0.001), indicating that high-dose APS inhibits inflammation and lipolysis reactions in adipocytes. The lipidomics results showed that high-dose APS intervention reduced the expression levels of 66 DELs, including ceramides and their modifications, triacylglycerols, etc. Metabolic pathway enrichment analysis showed that these DELs mainly involved glycerophospholipid metabolism and sphingolipid metabolism pathways. The transcriptomic results showed that the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) pathway was repeatedly enriched in DEGs, indicating that this pathway may be the core pathway for APS to function. In addition, the expressions of 18 DEGs was significantly down-regulated by APS, and the gene interaction network diagram showed that these genes had complex interactions with Akt. Western blotting results confirmed that APS intervention reversed the expression levels of Tribbles homologous protein 3 (TRIB3), phosphorylated Akt (p-Akt), phosphodiesterase 3B (PDE3B), phosphorylated protein kinase A (p-PKA), phosphorylated hormone sensitive lipase (p-HSL) and adipose triglyceride lipase (ATGL) (P < 0.05, 0.01, 0.001). Conclusion APS may alleviate inflammation in adipose tissue, reduce the synthesis of sphingolipids such as ceramides, regulate TRIB3-Akt axis, restore insulin resistance to lipolysis, promote lipid signaling, and improve the consumption of CC adipose tissue.

Key words

Astragalus polysaccharides / cancer cachexia / fat consumption / inflammation / glycerophospholipid metabolism / sphingolipid metabolism / TRIB3-Akt axis

引用本文

晁兴亮, 苏小宇, 田智涵, 李梓源, 刘雪, 曲一玮, 王咏, 马度芳. 基于脂质组学与转录组学探究黄芪多糖改善癌症恶病质脂肪组织消耗的作用机制. 中草药, 2026 , 57 (1) : 152 -163 . DOI: 10.7501/j.issn.0253-2670.2026.01.015

CHAO Xingliang, SU Xiaoyu, TIAN Zhihan, LI Ziyuan, LIU Xue, QU Yiwei, WANG Yong, MA Dufang. Mechanism of Astragalus polysaccharides in alleviating adipose tissue wasting in cancer cachexia based on lipidomics and transcriptomics[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (1) : 152 -163 . DOI: 10.7501/j.issn.0253-2670.2026.01.015

基金

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中国博士后科学基金第73批面上项目 (2023M732136); 国家自然科学基金面上项目 (82374376); 泰山学者工程专项经费资助 (tsqn202408382)

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2026年第57卷第1期

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doi: 10.7501/j.issn.0253-2670.2026.01.015

接收时间：2025-08-29
首发时间：2026-09-09

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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