Transcriptome Sequencing of Cecum Tissues Form Septic Rats Treated With or Without Tongfu Pingchuan Decoction

ABSTRACT: This study aimed to investigate the protective mechanisms of the Traditional Chinese Medicine Tongfu Pingchuan decoction (TFP) in the cecum of septic rats. Thirty rats were randomly divided into three groups: Sham, Model (sepsis induced by cecal ligation and puncture), and TFP (sepsis treated with TFP). Rats received 1 mL/kg TFP or PBS via gavage twice daily for one week, after which whole blood and cecum tissues were collected. Transcriptome sequencing was conducted on six cecum tissues per group. Bioinformatics analyses predicted the potential mechanisms of TFP, which were subsequently validated in cecum tissues and RAW264.7 cell cultures. We found that Pathways such as TNF signaling, complement and coagulation cascades, fatty acid metabolism, and PPAR signaling were activated, while cholinergic synapse, ECM-receptor interaction, and VSMC contraction were inhibited in the Model group compared to Sham. These changes were largely reversed in the TFP group. Chrm4 and Pygm were identified as potential TFP targets, as they were overlapping differentially expressed genes (DEGs) in the predicted TFP targets and an identified WGCNA module of interest. Chrm4 was downregulated in the Model group and restored by TFP treatment. In the Model group, M1 macrophages were induced, while M2 macrophages were suppressed. TFP inhibited M1 macrophages and further enhanced M2 macrophages. These effects were corroborated in LPS-stimulated RAW264.7 cells, where TFP also modulated cytokine levels (IL-6, IL-10, TNF-α). The effects of TFP were negated by Boc-2 (a PCTR1 inhibitor) or Chrm4 silencing. Additionally, TFP suppressed IL1RN, p-ERK2/ERK2, and p-AKT/AKT levels in LPS-treated RAW264.7 cells, but these effects were abolished upon Chrm4 silencing. Collectively, we show that TFP alleviates sepsis by promoting Chrm4/IL1RN-regulated macrophage polarization and facilitating inflammation resolution.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE290624 | GEO | 2026/02/01

REPOSITORIES: GEO