Ligustrazine nanoparticles inhibits epithelial-mesenchymal transition and alleviates postoperative abdominal adhesion.

Abstract

Following abdominal surgery, the occurrence of postoperative abdominal adhesion (PAA) is highly prevalent and stands out as one of the most frequently encountered complications. The effect and molecular mechanisms of Ligustrazine nanoparticles (LN) underlying epithelial-mesenchymal transition (EMT) in PAA still remain elusive. Adhesions were induced in Male Sprague-Dawley rats by injuring the cecum (cecal abrasion model), followed by administration of LN and hyaluronate acid (HA). The mechanism was further verified by enzyme-linked immunosorbent assay, wound healing assay, si-RNA and Western blot. Animal experiments revealed that LN effectively ameliorated adhesions, notably decreased tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-8, and fibrosis, and reduced the expression of TGF-β1 and EMT related markers (Fibronectin and E-cadherin). Furthermore, in vitro experiments demonstrated that LN might inhibit the TGF-β1 FOXC2 pathway through suppressing the expression of Fibronectin, P120, and E-cadherin and ameliorating peritoneal adhesion. Collectively, our findings indicate that LN inhibits PAA formation by reducing inflammation, decreasing EMT and promoting peritoneal mesothelial cell repair. Therefore, LN might be considered a potential candidate for the treatment of PPA. However, further clinical studies are required to approve the effectiveness of LN.