关键词: 乙型肝炎, 证候, 肝胆湿热, 脾胃湿热, 蛋白质类, 生物信息学

Abstract: Background　Liver-gallbladder damp-heat and spleen-stomach damp-heat syndromes，two most common syndromes in chronic hepatitis B（CHB），are difficult to be distinguished due to a similar manifestation of damp-heat.So finding the essence of difference and distinguishable biomarkers of them are of great significance to enrich the modern scientific connotation of TCM syndromes and improve the clinical precision differentiation and treatment.Objective　To investigate the differentially expressed proteins and their regulation as well as potentially distinguishable objective markers between liver-gallbladder damp-heat and spleen-stomach damp-heat syndromes in CHB.Methods　From the General Hospital of Western Theater Command PLA，30 hepatology and gastroenterology outpatients with CHB〔15 with liver-gallbladder damp-heat syndrome（subgroup A）and 15 with spleen-stomach damp-heat syndrome（subgroup B）〕，and 10 heath examinees（control group）were recruited during January 2018 to January 2019.ELISA was used to detect the target proteins and bioinformatics analysis was conducted，involving CEACAM1，MCP-1，SDF-1，ORM2，MSN，FCN2，VCAM-1，IGF-1，NOTCH2，β-APP，ACO1，SORD and ALDH1A1.ROC analysis was conducted to explore the value of differentially expressed proteins in distinguishing liver-gallbladder damp-heat and spleen-stomach damp-heat syndromes in CHB.Results　The mean expression levels of CEACAM1，MCP-1，SDF-1，ORM2，MSN，FCN2，VCAM-1，IGF-1，NOTCH2，β-APP，ACO1，SORD and ALDH1A1 in subgroups A and B were significantly lower than those in control group（P<0.05）.Subgroup B had higher mean expression levels of CEACAM1，MCP-1，MSN and VCAM-1，and lower mean expression levels of SDF-1，ORM2，FCN2，IGF-1，NOTCH2 and β-APP than subgroup A（P<0.05）.Taking inter-subgroup differences reaching a significance level of P<0.01 as a criterion to further screen the differentially expressed proteins，only CEACAM1，SDF-1，MSN and IGF-1 of above-mentioned 10 proteins were enrolled，specifically，subgroup B had higher mean expression levels of CEACAM1 and MSN and lower mean expression levels of SDF-1 and IGF-1（P<0.01）.Bioinformatics analysis results showed that，there were relatively close associations of CEACAM1，MCP-1，SDF-1，ORM2，MSN，FCN2，VCAM-1，IGF-1，NOTCH2 and β-APP between liver-gallbladder damp-heat and spleen-stomach damp-heat syndromes in CHB，moreover，the above-mentioned 10 differentially expressed proteins participated in multiple signaling pathways together.ROC curve analysis results showed that，in distinguishing the two syndromes，the AUC of CEACAM1 was 0.73〔95%CI（0.54，0.87）〕with sensitivity of 86.67% and specificity of 56.25%，the AUC of SDF-1 was 0.70〔95%CI（0.51，0.85）〕with sensitivity of 86.67% and specificity of 56.25%，and the AUC of MSN was 0.72〔95%CI（0.53，0.86）〕with sensitivity of 80.00% and specificity of 56.25%.Conclusion　Liver-gallbladder damp-heat and spleen-stomach damp-heat syndromes in CHB have objective differences，with CEACAM1，SDF-1，MSN and IGF-1 as major differentially expressed proteins.The biological mechanism for the differences may be correlated with oxidative stress response mediated by NF-κB and AGE-RAGE signaling pathways.Moreover，CEACAM1，SDF-1 and MSN may be used as potential biomarkers for distinguishing liver-gallbladder damp-heat and spleen-stomach damp-heat syndromes in CHB.

Key words: Chronic hepatitis B, Symptom complex, Liver-gallbladder damp-heat, Spleen-stomach damp-heat, Proteins, Bioinformatics