Objective To explore the metabolic differences between dry eye patients with Qi-Yin defi-ciency and heat stagnation in liver meridian patterns,and clarify their metabolic characteris-tics.Methods Patients with dry eye...Objective To explore the metabolic differences between dry eye patients with Qi-Yin defi-ciency and heat stagnation in liver meridian patterns,and clarify their metabolic characteris-tics.Methods Patients with dry eye who were treated in the Ophthalmology Ward and Outpatient Department of the First Hospital of Hunan University of Chinese Medicine from October 1,2020,to October 30,2021 were enrolled as the research participants in the study.They were assigned to two groups based on traditional Chinese medicine(TCM)syndrome types:heat stagnation in liver meridian pattern group and Qi-Yin deficiency pattern group.Healthy vol-unteers who underwent health check-ups in the Health Management Department were in-cluded as healthy group following the random number table method.The tears of the pa-tients and the healthy volunteer participants were tested by high-performance liquid chro-matography-mass spectrometry(LC-MS).The differential metabolites were screened out by multivariate statistical analysis,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment was performed on the differential metabolites.Finally,the association analysis of differential proteins and metabolites was conducted to verify and supplement the metabolites.Results A total of 32 dry eye patients were enrolled,including 16 cases with heat stagnation in liver meridian pattern and 16 cases with Qi-Yin deficiency pattern.Fourteen healthy volun-teers were included as healthy group.There were no significant differences in baseline char-acteristics among the three groups(P>0.05).A total of 412 biomarkers were determined in Qi-Yin deficiency pattern group,mainly including lipids,lipid-like molecules,organic acids and their derivatives,organic heterocyclic compounds,and nucleosides and their analogues.For heat stagnation in liver meridian pattern group,112 metabolites were determined,main-ly including organic acids and their derivatives,lipids,and lipid-like molecules.The KEGG enrichment results of pathways and the relative content analysis of differential markers de-monstrate that purine metabolism and caffeine metabolism pathways are common metabol-ic characteristics of all dry eyes.Among them,deoxyinosine monophosphate(dIMP)and 2-(formamido)-N1-(5-phospha-D-ribosyl)acetamidine can serve as their biomarkers.The main characteristics of Qi-Yin deficiency syndrome pattern were the significant enhancement of metabolic pathways such as lysine degradation,ovarian steroidogenesis,cholesterol metabolism,pyrimidine metabolism,and bile secretion(P<0.05).Dry eye associated with the heat stagnation in liver meridian pattern is mainly characterized by inhibition of the valine,leucine,and isoleucine biosynthesis pathways(P<0.05).Conclusion Metabolomics can be used as an effective basis for TCM syndrome classification.Different patterns of dry eye syndrome exhibit typical characteristics in the types and concen-trations of metabolites,which correspond to the syndrome classification in TCM.This study initially confirms the rationality of TCM syndrome classification and provides significant ref-erence for the mechanism of dry eye and drug development.展开更多
基金National Natural Science Foundation of China Project(82305037)Guiding Project for Innovative Clinical Medical Technology in Hunan Province(2021SK50809)Scientific Research Project of Hunan Administration of Traditional Chinese Medicine(D2022053).
文摘Objective To explore the metabolic differences between dry eye patients with Qi-Yin defi-ciency and heat stagnation in liver meridian patterns,and clarify their metabolic characteris-tics.Methods Patients with dry eye who were treated in the Ophthalmology Ward and Outpatient Department of the First Hospital of Hunan University of Chinese Medicine from October 1,2020,to October 30,2021 were enrolled as the research participants in the study.They were assigned to two groups based on traditional Chinese medicine(TCM)syndrome types:heat stagnation in liver meridian pattern group and Qi-Yin deficiency pattern group.Healthy vol-unteers who underwent health check-ups in the Health Management Department were in-cluded as healthy group following the random number table method.The tears of the pa-tients and the healthy volunteer participants were tested by high-performance liquid chro-matography-mass spectrometry(LC-MS).The differential metabolites were screened out by multivariate statistical analysis,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment was performed on the differential metabolites.Finally,the association analysis of differential proteins and metabolites was conducted to verify and supplement the metabolites.Results A total of 32 dry eye patients were enrolled,including 16 cases with heat stagnation in liver meridian pattern and 16 cases with Qi-Yin deficiency pattern.Fourteen healthy volun-teers were included as healthy group.There were no significant differences in baseline char-acteristics among the three groups(P>0.05).A total of 412 biomarkers were determined in Qi-Yin deficiency pattern group,mainly including lipids,lipid-like molecules,organic acids and their derivatives,organic heterocyclic compounds,and nucleosides and their analogues.For heat stagnation in liver meridian pattern group,112 metabolites were determined,main-ly including organic acids and their derivatives,lipids,and lipid-like molecules.The KEGG enrichment results of pathways and the relative content analysis of differential markers de-monstrate that purine metabolism and caffeine metabolism pathways are common metabol-ic characteristics of all dry eyes.Among them,deoxyinosine monophosphate(dIMP)and 2-(formamido)-N1-(5-phospha-D-ribosyl)acetamidine can serve as their biomarkers.The main characteristics of Qi-Yin deficiency syndrome pattern were the significant enhancement of metabolic pathways such as lysine degradation,ovarian steroidogenesis,cholesterol metabolism,pyrimidine metabolism,and bile secretion(P<0.05).Dry eye associated with the heat stagnation in liver meridian pattern is mainly characterized by inhibition of the valine,leucine,and isoleucine biosynthesis pathways(P<0.05).Conclusion Metabolomics can be used as an effective basis for TCM syndrome classification.Different patterns of dry eye syndrome exhibit typical characteristics in the types and concen-trations of metabolites,which correspond to the syndrome classification in TCM.This study initially confirms the rationality of TCM syndrome classification and provides significant ref-erence for the mechanism of dry eye and drug development.