Liver depression and spleen deficiency syndrome (LDSDS) and spleen-gastric damp-heat syndrome (SGDHS) are two major traditional Chinese medicine syndromes observed in chronic hepatitis B (CHB). Both syndromes exhibit significant differences in the pathogenesis and prognosis, and are closely related to the immune system. However, the underlying mechanisms are largely unknown. This study aimed to explore the immunoregulatory mechanisms of the two syndromes and promote the differentiation precision between the two syndromes. Thirty-six patients with CHB (18 LDSDS patients and 18 SGDHS patients) and 14 healthy controls were recruited into this study and blood was collected from all the subjects for testing. We studied the contents of T lymphocytes by flow cytometry and the expression levels of HMGB1/PTEN/PI3K axis proteins by enzyme-linked immunosorbent assay (Elisa). Protein-protein interaction (PPI) networks among HMGB1/PTEN/PI3K axis were constructed for functional enrichment. The correlations between T lymphocytes and proteins were analyzed by constructing multiple regression equations. The results revealed that the CD8+ T cells level in the two syndromes were lower than that in healthy controls, and the levels of Th17, Treg cells, and HMGB1, PI3K, PDK1, Akt were higher than those of the healthy controls (p < 0.05). Moreover, the levels of CD4+ T, Th17 cells, and HMGB1, PTEN, PI3K in LDSDS were higher than SGDHS (p < 0.05). PPI network indicated that HMGB1/PTEN/PI3K axis participated in T cell activation and liver pathology. Our results revealed that HMGB1/PTEN/PI3K axis may play an important role in regulating the formation of peripheral immune differences between the two syndromes. CD4+ T and Th17 are two representative immune cells that may serve as potential biological markers for LDSDS and SGDHS in CHB.
肝郁脾虚证和脾胃湿热证是慢性乙型肝炎的主要证型，二者在发病机制和预后方面存在明显差异，这可能与免疫调节密切相关，但其内在机制仍不清楚。本研究旨在更好地了解两证型的免疫调节机制，促进临床辨证分型。本研究共纳入了36例慢性乙型肝炎患者(肝郁脾虚证和脾胃湿热证各18例)和14例健康志愿者，并收集受试者的血液标本进行检测。研究通过流式细胞仪检测两证型和健康对照组的T淋巴细胞数量，Elisa检测HMGB1/PTEN/PI3K通路蛋白表达水平；构建蛋白关联网络，分析HMGB1/PTEN/PI3K轴的功能富集。构建多元回归方程分析T淋巴细胞和通路蛋白之间的相关性。结果显示两证型的CD8+ T细胞水平显著低于健康对照组，而Th17、Treg细胞和HMGB1、PI3K、PDK1、Akt的水平高于健康对照组 (p < 0.05)。两证型相比，肝郁脾虚证的CD4+ T、Th17细胞和HMGB1、PTEN、PI3K水平显著高于脾胃湿热证 (p < 0.05)。蛋白质互作网络图显示，HMGB/PTEN/PI3K轴参与了T细胞活化和肝病的病理过程。HMGB1/PTEN/PI3K轴可能在两证型的外周免疫差异形成中发挥着重要作用。CD4+ T和Th17细胞或许可以作为慢性乙型肝炎患者肝郁脾虚证和脾胃湿热证免疫差异的潜在生物学标志物。.
Keywords: HMGB1/PTEN/PI3K axis; HMGB1/PTEN/PI3K 轴; T lymphocyte; T淋巴细胞; chronic hepatitis B; liver depression and spleen deficiency syndrome; spleen-gastric damp-heat syndrome; 慢性乙型病毒性肝炎; 肝郁脾虚证; 脾胃湿热证.
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