外周血多组学综合分析慢性乙型肝炎不同苔色患者的病理基础

Yi-shuang TANG; Jian-chun GUO; Lin XU; Xiao-na ZHANG; Xiao-ping SHEN; Ya-mei HAI; Yu-feng MAO; Yi-yang HU; Yu ZHAO

doi:10.1007/s11655-020-3275-4

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外周血多组学综合分析慢性乙型肝炎不同苔色患者的病理基础

Original Article | Updated：2022-03-18

- 外周血多组学综合分析慢性乙型肝炎不同苔色患者的病理基础
- Pathological Change of Chronic Hepatitis B Patients with Different Tongue Coatings by Circular Multi-omics Integrated Analysis
- Chinese Journal of Integrative Medicine 2022年28卷第1期页码：28-35
- Affiliations：
  
  1.Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai (201203), China
  2.Department of Integrated Chinese and Western Medicine,Hangzhou Xixi Hospital, Hangzhou (310023), China
  3.National Engineering Center for Biochip at Shanghai, Shanghai (201203),China
  4.Institute of Clinical Pharmacology, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai (201203), China
  5.Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai (201203), China
- Author bio：
  
  Dr. ZHAO Yu, E-mail: cathy150@139.com
- Funds：
  
  the National Science and Technology Major Project of China(2017ZX09304002);the National Natural Science Foundation of China(81830119;81403298)
- DOI：10.1007/s11655-020-3275-4
  中图分类号：
- 纸质出版日期：2022-01-01，
  
  网络出版日期：2020-09-11，
  
  录用日期：2020-04-17
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Yi-shuang TANG, Jian-chun GUO, Lin XU, 等. 外周血多组学综合分析慢性乙型肝炎不同苔色患者的病理基础[J]. Chinese Journal of Integrative Medicine, 2022,28(1):28-35.

Yi-shuang TANG, Jian-chun GUO, Lin XU, et al. Pathological Change of Chronic Hepatitis B Patients with Different Tongue Coatings by Circular Multi-omics Integrated Analysis[J]. Chinese Journal of Integrative Medicine, 2022,28(1):28-35.
Yi-shuang TANG, Jian-chun GUO, Lin XU, 等. 外周血多组学综合分析慢性乙型肝炎不同苔色患者的病理基础[J]. Chinese Journal of Integrative Medicine, 2022,28(1):28-35. DOI： 10.1007/s11655-020-3275-4.

Yi-shuang TANG, Jian-chun GUO, Lin XU, et al. Pathological Change of Chronic Hepatitis B Patients with Different Tongue Coatings by Circular Multi-omics Integrated Analysis[J]. Chinese Journal of Integrative Medicine, 2022,28(1):28-35. DOI： 10.1007/s11655-020-3275-4.

摘要

目的:

中医药已被证实可有效防治慢性肝病

但中医理论的现代生物学基础尚缺乏阐释. 舌诊是中医的个性化诊疗的重要依据

本研究旨在比较慢性乙型肝炎 (CHB) 不同苔色患者的循环病理变化.

方法:

本研究将41例CHB白苔 (WTC) 及黄苔 (YTC) 患者纳入研究

并将14名正常舌象的健康志愿者作为对照. 通过转录组芯片检测受试者外周血白细胞mRNA表达

并随机选择9个mRNA进行芯片检测结果验证. 采用气相色谱-质谱法检测分析外周血代谢物谱变化. 采用IPA分析平台或在线代谢组学数据库进行生物信息分析

应用ClueGO构建生物网络.

结果:

与健康志愿者比较

在WTC和YTC患者中分别发现了945和716个差异基因. 通过对差异基因的功能富集分析发现

不论苔色表现如何

CHB患者的外周血中细胞死亡、细胞凋亡和坏死的相关生物功能明显增加 (Z评分≥2

0.05)

T淋巴细胞活化明显降低 (Z评分≤–2

0.05) . 与WTC患者相比

生物学分析预测提示YTC患者病毒复制更活跃

且循环中脂肪酸类

如油酸和月桂酸的含量和柠檬酸循环相关代谢产物的含量较高(

0.1). 基于差异基因和代谢物的综合分析表明

TRAF6介导的NF-κB活化过程可能是WTC和YTC患者之间生物学功能网络的最大差异.

结论:

本研究结果提示

慢性乙型肝炎黄苔患者较白胎患者具有更严重的炎症和脂肪酸代谢紊乱. 研究结果为中医舌诊理论的现代病理学诠释提供了参考依据.

Abstract

Objective:

To compare the circular pathological changes of chronic hepatitis B (CHB) patients according to the tongue diagnosis.

Methods:

Totally 41 CHB patients with typical white tongue coating (WTC) or yellow tongue coating (YTC) were enrolled and 14 healthy volunteers with normal tongue manifestation served as controls. The mRNA expression of peripheral leukocytes was detected by GeneChips

and 9 genes were randomly selected for expression validation. Circular metabolites were detected by gas chromatographymass spectrometry. Biological information was analyzed based on ingenuity pathways analysis or metabolomics database and the integrated networks were constructed by ClueGO.

Results:

A total of 945 and 716 differentially expressed genes were found in patients with WTC and YTC relative to healthy volunteers respectively. The biological information analysis indicated that CHB patients had obviously increased functions in cell death

apoptosis and necrosis (Z-score ≥2

0.05) and decreased activation in T lymphocytes (Z-score ≤–2

0.05)

regardless of the tongue manifestation. Compared to patients with WTC

the YTC patients were predicted to be more active in functions related to virus replication (Z-score ≥2

0.05)

and the content of circular fatty acids

such as oleic acid (

=0.098) and lauric acid (

=0.035)

and citric acid cycle-related metabolites were higher in the YTC patients (

0.1). The integrated analysis based on differential genes and metabolites indicated that the most difference in the biological function network between the WTC and YTC patients was tumor necrosis factor receptor associated factor 6 mediated-nuclear factor kappa-B activation process.

Conclusions:

CHB patients with YTC had more severe inflammation and fatty acids metabolism aberrant than patients with WTC. The results facilitate the modern pathological annotation of Chinese medicine tongue diagnosis theory and provide a reference for the interpretation of pharmacological mechanisms of Chinese medicine treatment.

关键词

Keywords

Chinese medicinechronic hepatitis Btongue diagnosismetabolomicstranscriptomic

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