中华中医药学刊

基于“肠-肾轴”的泽泻致肾损伤及在六味地黄丸配伍中的肾脏保护机制研究

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王萌萌 ¹ , 方健 ²^,³ , 栾相佳 ⁴ , 崔鑫 ¹ , 孟庆刚 ² , 王连心 ¹

中华中医药学刊 | 国家项目点击 2026,44(1): 121-127

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中华中医药学刊 |国家项目点击 2026 , 44 (1) : 121 -127

基于“肠-肾轴”的泽泻致肾损伤及在六味地黄丸配伍中的肾脏保护机制研究

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王萌萌¹, 方健²^,³, 栾相佳⁴, 崔鑫¹, 孟庆刚², 王连心¹

作者信息

^1.中国中医科学院中医临床基础医学研究所，北京 100700

^2.北京中医药大学，北京 100029

^3.唐山师范学院，河北唐山 063000

^4.中国中医科学院广安门医院，北京 100053

Exploring Renal Damage Caused by Zexie（Alismatis Rhizoma）and Its Renal Protective Mechanism in Combination of Liuwei Dihuang Pills（六味地黄丸）from Perspective of “Gut-Kidney Axis”

Mengmeng WANG¹, Jian FANG²^,³, Xiangjia LUAN⁴, Xin CUI¹, Qinggang MENG², Lianxin WANG¹

Affiliations

^1.Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China

^2.Beijing University of Chinese Medicine, Beijing 100029, China

^3.Tangshan Normal University, Tangshan 063000, Hebei, China

^4.Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China

出版时间: 2026-01-10 doi: 10.13193/j.issn.1673-7717.2026.01.026

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摘要

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目的

泽泻的某些成分具有肾毒性，可能通过肠道菌群导致肾脏损伤。六味地黄丸的配伍中，其他药材的药理作用可能减轻或抵消泽泻的肾毒性，从而发挥整体的肾脏保护作用。因此需要从“肠-肾轴”角度下探究泽泻致药物性肾损伤的机制及六味地黄丸复方对肾脏疾病保护性机制。

方法

研究通过网络毒理学的方法，筛选泽泻致肾损伤的潜在靶点，以及通过网络药理学的方法筛选六味地黄丸保护肾损伤的潜在靶点。此外采用孟德尔随机化方法进行菌群与肾脏损伤疾病之间因果推断分析，于NCBI以及3DSNP网站查询显著单核苷酸多态性（single nucleotide polymorphism，SNP）邻近的相关基因，最终与药物的潜在靶点构建蛋白互作网络（protein-protein interaction，PPI）探究泽泻在六味地黄丸配伍中减轻肾损伤的机制。

结果

泽泻在中药系统毒理学数据库（traditional Chinese medicine system toxicology database，TCMSTD）平台筛选后获得15种毒性成分，泽泻毒性成分靶点与肠道菌群失调综合征和肾损伤的交集靶点为HSPA5，此外，在中药系统药理学数据库与分析平台（traditional Chinese medicine systems pharmacology database and analysis platform，TCMSP）共获得66种六味地黄丸的活性成分，而六味地黄丸成分靶点与肠道菌群失调综合征和肾损伤共得到共同靶点27个。通过孟德尔随机化探讨了肠道菌群致肾损伤的因果关系，揭示了Marvinbryantia（马文布赖恩特菌属）、Lachnospiraceae（紫胶螺科菌）、Porphyromonadaceae（卟啉单胞菌科）、Coprococcus1（粪球菌属1）可导致肾脏损伤（OR>1）。PPI网络中菌群显著的SNP所邻近的基因HSPA5与泽泻致肾损伤的靶点具有蛋白互作作用，表明泽泻可能通过调控这类肠道菌群导致肾损伤。通过孟德尔随机化探讨了肠道菌群与肾损伤的因果关系，在对肾脏损伤具有保护性的肠道菌群中，有15种菌群对肾脏损伤具有保护性作用（OR<1）。PPI网络中菌群显著的SNP所邻近的基因TNF degree值最高，与六味地黄丸对肾损伤起到保护性作用的靶点具有蛋白互作作用。

结论

从“肠-肾轴”的角度，泽泻具有通过调控HSPA5导致药物性肾损伤的机制，但六味地黄丸通过复方配伍调控TNF反而对肾脏具有保护作用，阐明了经典名方六味地黄丸的疗效及安全性机制。

关键词

肠道菌群 / 孟德尔随机化 / 泽泻 / 六味地黄丸

Abstract

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Objective

Some components of Zexie（Alismatis Rhizoma）are nephrotoxic and may cause kidney injury through intestinal flora. In the combination of Liuwei Dihuang Pills（六味地黄丸），the pharmacological effects of the other medicinal materials may reduce or offset the nephrotoxicity of Zexie（Alismatis Rhizoma），thereby exerting an overall kidney protective effect. Therefore，it is necessary to explore the mechanism of drug-induced kidney injury caused by Zexie（Alismatis Rhizoma）and the protective mechanism of Liuwei Dihuang Pills on kidney disease from the perspective of the “gut-kidney axis”.

Methods

In this study，the potential target of kidney injury induced by Zexie（Alismatis Rhizoma）was screened by network toxicology，and the potential target of Liuwei Dihuang Pills for protecting kidney injury was screened by network pharmacology. In addition，Mendelian randomization method was used to conduct the causal inference analysis between microbiota and kidney injury diseases. Relevant genes adjacent to significant single nucleotide polymorphisms（SNPs）were searched on NCBI and 3DSNP websites. Finally，protein-protein interaction（PPI）network was constructed with potential drug targets to explore the mechanism of reducing kidney injury caused by Zexie（Alismatis Rhizoma）combined with Liuwei Dihuang Pills.

Result

After screening on the traditional Chinese medicine system toxicology database（TCMSTD）platform，15 toxic components were obtained，and the overlap target of toxic components of Zexie（Alismatis Rhizoma）with intestinal flora dysregulation syndrome and kidney injury was HSPA5. In addition，66 active components of Liuwei Dihuang Pills were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP），and 27 common targets were obtained with intestinal flora dysregulation syndrome and kidney injury. Through Mendelian randomization，the causal relationship of intestinal flora induced kidney injury was investigated. Marvinbryantia，Lachnospiraceae，Porphyromonadaceae and Coprococcus1（OR>1）were found to cause kidney injury. The gene HSPA5 located in the significant SNP of the flora in the PPI network had protein interaction with the target of kidney injury caused by Zexie（Alismatis Rhizoma），indicating that Zexie（Alismatis Rhizoma）may cause kidney injury by regulating such intestinal flora. The causal relationship between intestinal flora and kidney injury was investigated by Mendelian randomization. Among the intestinal flora that had protective effects on kidney injury，there were 15 types of flora that had protective effects on kidney injury（OR<1）. In the PPI network，the gene with significant bacterial SNPS had the highest TNF degree，which had protein interaction with the target of Liuwei Dihuang Pill protective effect on kidney injury.

Conclusion

From the perspective of the “gut-kidney axis”，Zexie（Alismatis Rhizoma）has the mechanism of drug-induced kidney injury through regulation of HSPA5，but Liuwei Dihuang Pills have a protective effect on kidney through regulation of TNF through combination，which illustrates the efficacy and safety mechanism of Liuwei Dihuang Pills.

Key words

intestinal flora / Mendelian randomization / Zexie（Alismatis Rhizoma） / Liuwei Dihuang Pills（六味地黄丸）

引用本文

王萌萌, 方健, 栾相佳, 崔鑫, 孟庆刚, 王连心. 基于“肠-肾轴”的泽泻致肾损伤及在六味地黄丸配伍中的肾脏保护机制研究. 中华中医药学刊, 2026 , 44 (1) : 121 -127 . DOI: 10.13193/j.issn.1673-7717.2026.01.026

Mengmeng WANG, Jian FANG, Xiangjia LUAN, Xin CUI, Qinggang MENG, Lianxin WANG. Exploring Renal Damage Caused by Zexie（Alismatis Rhizoma）and Its Renal Protective Mechanism in Combination of Liuwei Dihuang Pills（六味地黄丸）from Perspective of “Gut-Kidney Axis”[J]. Chinese Archives of Traditional Chinese Medicine, 2026 , 44 (1) : 121 -127 . DOI: 10.13193/j.issn.1673-7717.2026.01.026

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2026年第44卷第1期

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doi: 10.13193/j.issn.1673-7717.2026.01.026

首发时间：2026-10-14
出版时间：2026-01-10

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^1.中国中医科学院中医临床基础医学研究所，北京 100700

^2.北京中医药大学，北京 100029

^3.唐山师范学院，河北唐山 063000

^4.中国中医科学院广安门医院，北京 100053

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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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