title: Elevation of HO-1 Expression Mitigates Intestinal Ischemia-Reperfusion Injury and Restores Tight Junction Function in a Rat Liver Transplantation Model.
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.
authors.affiliation: Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Xinjin
authors.initials: X
authors.lastname: Chi
authors.affiliation: Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yao
authors.affiliation: Department of Anesthesiology, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xia
authors.affiliation: Department of Pathology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Breast and Thyroid Surgery, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Hei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D051547:Heme Oxygenase-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology; D007249:Inflammation / Q000517:prevention & control; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D062793:Occludin / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; D062793:Occludin; D011524:Protoporphyrins; D062826:Zonula Occludens-1 Protein; C017803:zinc protoporphyrin; D008315:Malondialdehyde; D006427:Hemin; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D053148:Caspase 3