多组学驱动的中医证诊断与治疗模型构建范式——以湿证为例

Multi-omics driven paradigm for construction of traditional Chinese Medicine Zheng (syndrome) diagnosis and treatment model, taking Shi Zheng (syndrome of dampness) as an example.

作者信息

Wang Wenkai, Yang Le, Li Wanhua, Sun Ye, Sun Hui, Chen Yanjia, Ren Junling, Guo Jianwen, Wei Shuyun, Lin Fengye, Yan Guangli, Han Ying, Chen Qubo, Wang Xijun

机构信息

State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Dade Road 111, Guangzhou, 510000, China.

State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China.

出版信息

Chin Med. 2025 Mar 8;20(1):33. doi: 10.1186/s13020-025-01085-2.

DOI:10.1186/s13020-025-01085-2

PMID:40057776

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11890557/

Abstract

BACKGROUND

Shi Zheng (SZ, syndrome of dampness) is a major syndrome type in traditional Chinese Medicine (TCM), the ambiguity of its pathomechanism and the lack of blood diagnostic indicators have limited the understanding of the development of SZ.

PURPOSE

To explore the pathological mechanism of SZ and establish a symptom-centered diagnosis and treatment model.

METHODS

We recruited 250 participants, including healthy individuals and patients diagnosed with SZ. Serum metabolomics and proteomics analyses were performed to screen common pathways. Along with the biological significance of common pathways, a common pathway-symptom correlation diagram was constructed to elucidate the pathological mechanism underlying the occurrence and development of SZ. The enrichment score and correlations with SZ main symptom was used to screen the key common pathways. The key common pathways related to differential metabolites and proteins were used to establish a multi-index diagnostic model and protein therapy target group.

RESULTS

Joint metabolomics and proteomics analyses revealed 18 common pathways associated with symptoms. Six key pathways, such as pathogenic Escherichia coli infection, rheumatoid arthritis, PPAR signaling pathway, bile secretion, GnRH signaling pathway, and fat digestion and absorption were correlated with the main symptoms of SZ. These symptoms included greasy/thick/slippery tongue coating, heavy head, heavy body, heavy limbs, heavy joints, greasy hair, sticky mouth, sticky stool, and damp scrotum. Moreover, seven differential metabolites related to the key pathways were identified: LysoPA (20:3(5Z,8Z,11Z)/0:0), prostaglandin E2, leukotriene B4, lithocholate 3-O-glucuronide, 3-hydroxyquinine, lithocholic acid glycine conjugate, and PA(18:0/22:6(5Z,8E,10Z,13Z,15E,19Z)-2OH(7S, 17S)), and the combined diagnostic value of the seven indicators was the highest (discovery cohort: AUC = 0.90; validation cohort: AUC = 0.99). There were 23 differential proteins related to the key pathways, and six protein targets were identified, including RHOA, TNFSF13, PRKCD, APOA2, ATP1A1, and FABP1.

CONCLUSION

The combined analysis of metabolomics and proteomics established a symptom-centered diagnosis and treatment model of Shi Zheng.

摘要

背景

湿证是中医主要证型之一，其病机的模糊性以及缺乏血液诊断指标限制了对湿证发生发展的认识。

目的

探索湿证的病理机制并建立以症状为中心的诊疗模型。

方法

招募250名参与者，包括健康个体和诊断为湿证的患者。进行血清代谢组学和蛋白质组学分析以筛选共同通路。结合共同通路的生物学意义，构建共同通路-症状关联图以阐明湿证发生发展的病理机制。利用富集分数和与湿证主要症状的相关性筛选关键共同通路。与差异代谢物和蛋白质相关的关键共同通路用于建立多指标诊断模型和蛋白质治疗靶点组。

结果

代谢组学和蛋白质组学联合分析揭示了18条与症状相关的共同通路。六条关键通路，如致病性大肠杆菌感染、类风湿关节炎、PPAR信号通路、胆汁分泌、GnRH信号通路以及脂肪消化与吸收，与湿证的主要症状相关。这些症状包括舌苔腻/厚/滑、头重、身重、四肢沉重、关节沉重、头发油腻、口黏、便黏以及阴囊潮湿。此外，鉴定出了与关键通路相关的七种差异代谢物：溶血磷脂酸（20:3(5Z,8Z,11Z)/0:0）、前列腺素E2、白三烯B4、石胆酸3-O-葡萄糖醛酸、3-羟基喹啉、石胆酸甘氨酸共轭物以及PA(18:0/22:6(5Z,8E,10Z,13Z,15E,19Z)-2OH(7S,17S))，这七种指标的联合诊断价值最高（发现队列：AUC = 0.90；验证队列：AUC = 0.99）。有23种与关键通路相关的差异蛋白质，鉴定出六个蛋白质靶点，包括RHOA、TNFSF13、PRKCD、APOA2、ATP1A1和FABP1。