School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Anat Rec (Hoboken). 2023 Dec;306(12):3085-3096. doi: 10.1002/ar.24899. Epub 2022 Feb 28.
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（CHB）的两种主要中医证候。两种证候在发病机制和预后方面存在显著差异，与免疫系统密切相关，但具体机制尚不清楚。本研究旨在探讨两种证候的免疫调节机制，提高两种证候的辨证精度。共纳入 36 例 CHB 患者（肝郁脾虚证 18 例，脾胃湿热证 18 例）和 14 例健康对照者，采集所有研究对象的血液进行检测。采用流式细胞术检测 T 淋巴细胞含量，酶联免疫吸附试验（ELISA）检测 HMGB1/PTEN/PI3K 轴蛋白表达水平。构建 HMGB1/PTEN/PI3K 轴蛋白互作网络，进行功能富集分析。构建多元回归方程分析 T 淋巴细胞与蛋白之间的相关性。结果显示，两种证候的 CD8+T 细胞水平低于健康对照组，Th17、Treg 细胞及 HMGB1、PI3K、PDK1、Akt 水平均高于健康对照组（p<0.05）。此外，肝郁脾虚证的 CD4+T、Th17 细胞及 HMGB1、PTEN、PI3K 水平均高于脾胃湿热证（p<0.05）。PPI 网络分析表明，HMGB1/PTEN/PI3K 轴参与 T 细胞活化及肝脏病理过程。本研究结果表明，HMGB1/PTEN/PI3K 轴可能在调节两种证候外周免疫差异形成中发挥重要作用。CD4+T、Th17 是两种代表性免疫细胞，可能成为 CHB 肝郁脾虚证和脾胃湿热证的潜在生物学标志物。
