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

Author:

Chi Xinjin1,Yao Weifeng1,Xia Hua2,Jin Yi3,Li Xi4,Cai Jun1,Hei Ziqing1

Affiliation:

1. Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510630, China

2. Department of Anesthesiology, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China

3. Department of Pathology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510630, China

4. Department of Breast and Thyroid Surgery, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510630, China

Abstract

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.

Funder

National Natural Science Foundation of China

Publisher

Hindawi Limited

Subject

Cell Biology,Ageing,General Medicine,Biochemistry

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