Intraperitoneal administration of activated protein C prevents postsurgical adhesion band formation

Area of Science:

• Biomedical research
• Surgical innovation
• Inflammation and immunology

Background:

• Postsurgical peritoneal adhesions are a significant cause of morbidity, including intestinal obstruction, pelvic pain, and infertility.
• Current treatments like Seprafilm have limitations, necessitating the exploration of novel therapeutic strategies.

Purpose of the Study:

• To evaluate the efficacy of activated protein C (APC) in preventing postsurgical peritoneal adhesions compared to a standard antiadhesion agent.
• To elucidate the mechanism underlying APC's protective effects in a murine adhesion model.

Main Methods:

• A mouse model of postsurgical peritoneal adhesion was established.
• Animals received intraperitoneal administration of either APC or sodium hyaluronate/carboxymethylcellulose (Seprafilm).
• Adhesion bands, inflammation scores, and peritoneal fluid markers (tPA, d-dimer, thrombin-antithrombin complex, cytokines) were assessed.

Main Results:

• APC significantly reduced the severity of postsurgical adhesion bands compared to Seprafilm.
• APC treatment led to lower inflammation scores and reduced concentrations of proinflammatory cytokines.
• Elevated tissue plasminogen activator (tPA) levels were observed in the APC-treated group.
• The protective effect of APC was dependent on its interaction with the endothelial protein C receptor (EPCR) and its signaling activity.

Conclusions:

• Activated protein C demonstrates superior efficacy in preventing postsurgical peritoneal adhesions compared to Seprafilm in a mouse model.
• APC's anti-adhesion properties are primarily mediated by its EPCR-dependent signaling pathway.
• APC holds significant therapeutic potential for the prevention of postsurgical adhesions.