Elevation of HO-1 Expression Mitigates Intestinal Ischemia-Reperfusion Injury and Restores Tight Junction Function in a Rat Liver Transplantation Model

Abstract EN

Aims.

This study was aimed at investigating whether elevation of heme oxygenase-1 (HO-1) expression could lead to restoring intestinal tight junction (TJ) function in a rat liver transplantation model.

Methods.

Intestinal mucosa injury was induced by orthotopic autologous liver transplantation (OALT) on male Sprague-Dawley rats.

Hemin (a potent HO-1 activator) and zinc-protoporphyrin (ZnPP, a HO-1 competitive inhibitor), were separately administered in selected groups before OALT.

The serum and intestinal mucosa samples were collected at 8 hours after the operation for analysis.

Results.

Hemin pretreatment significantly reduced the inflammation and oxidative stress in the mucosal tissue after OALT by elevating HO-1 protein expression, while ZnPP pretreatment aggravated the OALT mucosa injury.

Meanwhile, the restriction on the expression of tight junction proteins zonula occludens-1 and occludin was removed after hemin pretreatment.

These molecular events led to significant improvement on intestinal barrier function, which was proved to be through increasing nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and reducing nuclear translocation of nuclear factor kappa-B (NF-κB) in intestinal injured mucosa.

Summary.

Our study demonstrated that elevation of HO-1 expression reduced the OALT-induced intestinal mucosa injury and TJ dysfunction.

The HO-1 protective function was likely mediated through its effects of anti-inflammation and antioxidative stress.