Tanshinone IIA Improves Intestinal Barrier Integrity in Septic Rats.

Abstract

Aims: The present work aimed to examine impact of tanshinone IIA on intestinal barrier in sepsis and to explore the underpinning mechanisms. Materials and Methods: Sepsis induction in Sprague-Dawley (SD) rats was conducted via cecal ligation and puncture (CLP), with subsequent intraperitoneal injection of tanshinone IIA. Intestinal permeability was examined 12 h post-operation using the fluorescein isothiocyanate dextran method. Blood and distal ileum tissue samples were collected for Enzyme-Linked Immunosorbent Assay (ELISA) analysis of oxidative stress and inflammatory markers. Histopathologic examination was performed using hematoxylin and eosin staining and the Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) assay. Immunofluorescence and immunoblot were performed for protein detection. In vitro, Caco-2 cells were administered lipopolysaccharide (LPS) followed by tanshinone IIA treatment, and pregnane X receptor (PXR) and cytochrome P450-3A4 (CYP3A4) protein levels were assessed. Results: In sepsis model rats, tanshinone IIA dose-dependently reversed the increased intestinal permeability, bacterial shift rate, ileum Chiu's score, apoptosis level of ileal mucosa, the elevated serum and ileal Malondialdehyde (MDA), Interleukin-1 beta (IL-1β), and Tumor Necrosis Factor-alpha (TNF-α) amounts, and the enhanced ileal expression levels of Proto-oncogene c-Fos (c-Fos) and tryptase proteins. In addition, tanshinone IIA restored the decreased serum and ileal Superoxide Dismutase (SOD) levels and reversed the reduced ileal expression levels of claudin-1, Junctional Adhesion Molecule (JAM), occludin, and ZO-1. In vitro, tanshinone IIA restored PXR and CYP3A4 levels following LPS stimulation. Conclusion: Tanshinone IIA exerts a protective effect in murine CLP-induced sepsis. The underlying mechanism may involve activation of the PXR-CYP3A4 pathway in murine intestinal epithelial cells.