中华中医药学刊

整合肠道菌群和代谢组学探究山茱萸多糖干预2型糖尿病的作用机制

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张文静 ¹ , 尚子慧 ¹ , 孙孝亚 ¹ , 陈随清 ¹^,² , 崔永霞 ¹ , 吴明侠 ¹

中华中医药学刊 | 国家项目点击 2026,44(9): 19-24

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中华中医药学刊 |国家项目点击 2026 , 44 (9) : 19 -24

整合肠道菌群和代谢组学探究山茱萸多糖干预2型糖尿病的作用机制

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张文静¹, 尚子慧¹, 孙孝亚¹, 陈随清¹^,², 崔永霞¹, 吴明侠¹

作者信息

^1.河南中医药大学药学院，河南　郑州　450046

^2.河南中医药大学豫药全产业链研发河南省协同创新中心，河南　郑州　450046

通讯作者:

崔永霞（1979-），女，河南商丘人，副教授，硕士研究生导师，博士，研究方向：中药药效物质基础及药品质量评价。E-mail：1020076356@qq.com。

吴明侠（1971-），女，浙江东阳人，副教授，硕士研究生导师，博士，研究方向：中药质量分析及药效物质基础。E-mail：mxwu711@163.com。

作者简介:

张文静（2000-），女，河南南阳人，硕士在读，研究方向：中药药效物质基础及中药质量控制。

Exploring Mechanism of Shanzhuyu (Corni Fructus) Polysaccharides Integrating in Type 2 Diabetes Based on Intestinal Flora and Metabolomics

Wenjing ZHANG¹, Zihui SHANG¹, Xiaoya SUN¹, Suiqing CHEN¹^,², Yongxia CUI¹, Mingxia WU¹

Affiliations

^1.College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, Henan, China

^2.Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine, Zhengzhou 450046, Henan, China

出版时间: 2026-09-10 doi: 10.13193/j.issn.1673-7717.2026.09.004

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摘要

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目的

基于肠道菌群-宿主代谢，深入探究山茱萸多糖干预2型糖尿病的作用机制。

方法

采用高糖高脂饲料结合小剂量腹腔注射链脲佐菌素（Streptozocin，STZ）的方法建立2型糖尿病模型。对各组大鼠药效指标进行检测，利用16S rDNA测序技术检测各组大鼠肠道菌群结构，结合GC-MS技术测定短链脂肪酸（Short-Chain Fatty Acids，SCFAs）的含量，并采用Western Blot方法检测肝脏组织中G蛋白偶联受体43（G-Protein coupled Receptor 43，GPR43）、G蛋白偶联受体41（G-Protein coupled Receptor 41，GPR41）、胰高血糖素样肽-1（Glucagon-Like Peptide-1，GLP-1）蛋白水平。使用UPLC-MS/MS技术对各组动物粪便进行小分子代谢组学研究，对肠道菌群与差异代谢物进行相关性分析。

结果

药效指标检测结果显示，山茱萸多糖能显著降低2型糖尿病大鼠的血糖、血脂和炎症因子水平；肠道菌群测序结果显示，山茱萸多糖对2型糖尿病大鼠的菌群多样性有显著改善，门水平上，对厚壁菌门、拟杆菌门、疣微菌门和放线菌门丰度均有不同程度回调，厚壁菌门/拟杆菌门的比值显著升高（P<0.05）；属水平上，乳杆菌属、阿克曼氏菌、拟杆菌属和Muribaculaceae丰度均有所增加；SCFAs及关键代谢通路测定结果显示，2型糖尿病大鼠粪便中SCFAs含量均显著下降（P<0.01），GPR43、GPR41、GLP-1蛋白表达显著降低（P<0.01），山茱萸多糖干预后，SCFAs含量均显著增加（P<0.05，P<0.01），GPR41、GPR43、GLP-1蛋白表达显著升高（P<0.01）；代谢组学筛选出46个模型组和对照组组间显著变化（P<0.05）的差异代谢物，主要富集到鞘脂代谢、类固醇生物合成等19条代谢通路；联合分析结果显示，肠道菌群对鞘氨醇等差异代谢物具有显著调节作用，涉及鞘脂代谢和类固醇生物合成等代谢通路。

结论

山茱萸多糖可以通过调节肠道菌群结构影响SCFAs、鞘氨醇等代谢物水平，进而调节短链脂肪酸代谢、鞘脂代谢和类固醇生物合成等代谢通路，提高GPR43、GPR41、GLP-1蛋白的表达，调节大鼠的血糖血脂水平，从而调节糖脂代谢及肠道紊乱，抑制机体炎症反应，减轻胰岛素抵抗，发挥治疗2型糖尿病的作用。

关键词

山茱萸多糖 / 肠道菌群 / 短链脂肪酸 / 代谢组学 / 2型糖尿病

Abstract

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Objective

This study is based on intestinal flora-host metabolism and deeply explores the mechanism of Shanzhuyu (Corni Fructus) polysaccharides in type 2 diabetes.

Methods

A type 2 diabetes model was established by high sugar and high fat feed combined with a small dose of intraperitoneal injection of streptozocin (STZ). The pharmacoefficiency index of the rats in each group was detected, and the intestinal microbial structure of the rats in each group was detected by 16S rDNA sequencing technology, and the content of short-chain fatty acids (SCFAs) was measured in combination with GC-MS technology. The Western Blot method was used to detect the protein levels of G-protein coupled receptor 43 (GPR43), G-protein coupled receptor 41 (GPR41) and glucagon-like peptide-1 (GLP-1) in liver tissues. Small molecule metabolomics study was performed on animal feces in each group using UPLC-MS/MS technology, and the correlation analysis was conducted on intestinal microbiota and differential metabolites.

Results

The results of the drug efficacy index test showed that Shanzhuyu (Corni Fructus) polysaccharides could significantly reduce the blood sugar, blood lipids and inflammatory factors in the rats with type 2 diabetes. The results of intestinal flora sequencing showed that Shanzhuyu (Corni Fructus) polysaccharides significantly improved the bacterial diversity of type 2 diabetes rats. At the level of phylum, the abundance of Firmicutes, Bacteroides, Varves and Actinomycetes all had different degrees of correction, and the ratio of Firmicutes/Bacteroides increased significantly (P<0.05). At the level of genus, Lactobacillus, Akermans, Bacteroides and Muribaculaceae increased. The results of SCFAs and key metabolic pathways showed that the content of SCFAs in the feces of type 2 diabetes rats had significantly decreased (P<0.01), the protein expressions of GPR43, GPR41 and GLP-1 were significantly reduced (P<0.01), and after the intervention of Shanzhuyu (Corni Fructus) polysaccharides, the SCFAs content was significantly increased (P<0.05, P<0.01), and the protein expressions of GPR41, GPR43 and GLP-1 were significantly increased (P<0.01). Metabolomics screened differential metabolites with significant changes (P<0.05) among 46 model and control groups, mainly enriched 19 metabolic pathways such as sphingolipid metabolism and steroid biosynthesis. The results of the joint analysis showed that intestinal flora had a significant regulatory effect on differential metabolites such as sphingolipid metabolism and steroid biosynthesis, involving metabolic pathways such as sphingolipid metabolism and steroid biosynthesis.

Conclusion

Shanzhuyu (Corni Fructus) polysaccharides can affect the levels of metabolites such as SCFAs and sphingosine by regulating the intestinal microbiota structure, and then regulate the metabolism pathways such as short-chain fatty acid metabolism, sphingolipid metabolism and steroid biosynthesis, improve the protein expressions of GPR43, GPR41 and GLP-1, regulate the blood sugar and blood lipid levels of the rats, thereby regulating glycolipid metabolism and intestinal disorders, inhibiting the body's inflammatory response, reducing insulin resistance and playing a role in treating type 2 diabetes.

Key words

Shanzhuyu (Corni Fructus) polysaccharides / intestinal flora / short-chain fatty acids / metabolomics / type 2 diabetes mellitus

引用本文

张文静, 尚子慧, 孙孝亚, 陈随清, 崔永霞, 吴明侠. 整合肠道菌群和代谢组学探究山茱萸多糖干预2型糖尿病的作用机制. 中华中医药学刊, 2026 , 44 (9) : 19 -24 . DOI: 10.13193/j.issn.1673-7717.2026.09.004

Wenjing ZHANG, Zihui SHANG, Xiaoya SUN, Suiqing CHEN, Yongxia CUI, Mingxia WU. Exploring Mechanism of Shanzhuyu (Corni Fructus) Polysaccharides Integrating in Type 2 Diabetes Based on Intestinal Flora and Metabolomics[J]. Chinese Archives of Traditional Chinese Medicine, 2026 , 44 (9) : 19 -24 . DOI: 10.13193/j.issn.1673-7717.2026.09.004

基金

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国家重点研发计划项目(2023YFC3504000)
河南省重大科技专项(221100310400)
河南省科技发展计划项目(242102310524)
郑州市科技协同创新项目(2023XTCX053)
河南中医药大学博士科研基金项目(BSJJ2022-04)

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2026年第44卷第9期

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文章信息

doi: 10.13193/j.issn.1673-7717.2026.09.004

首发时间：2026-10-20
出版时间：2026-09-10

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出版历史

基金

国家重点研发计划项目(2023YFC3504000)

河南省重大科技专项(221100310400)

河南省科技发展计划项目(242102310524)

郑州市科技协同创新项目(2023XTCX053)

河南中医药大学博士科研基金项目(BSJJ2022-04)

作者信息

^1.河南中医药大学药学院，河南　郑州　450046

^2.河南中医药大学豫药全产业链研发河南省协同创新中心，河南　郑州　450046

通讯作者:

崔永霞（1979-），女，河南商丘人，副教授，硕士研究生导师，博士，研究方向：中药药效物质基础及药品质量评价。E-mail：1020076356@qq.com。

吴明侠（1971-），女，浙江东阳人，副教授，硕士研究生导师，博士，研究方向：中药质量分析及药效物质基础。E-mail：mxwu711@163.com。

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https://castjournals.cast.org.cn/joweb/zhzyyxk/CN/10.13193/j.issn.1673-7717.2026.09.004

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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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