Objective: To investigate the role of heme oxygenase-1 (HO-1) in the oxidative stress damage of intestinal mucosa barrier disruption in patients with malignant obstructive jaundice (MOJ).
Methods: Fifteen jaundiced patients with malignant biliary obstruction undergoing endoscopic retrograde cholangiopancreatography (ERCP) examination or treatment were enrolled. The control group was comprised of 10 healthy subjects with gastroscopy and 10 patients with non-jaundiced biliary obstruction. Patients were subjected to duodenal biopsy to assess the intestinal oxidative stress as estimated by lipid peroxidation (malondialdehyde) and activity of superoxide dismutase (SOD). Apoptosis of epithelial cell was examined by TdT-mediated dUTP-biotin nick end labeling. Immunohistochemistry and Western blotting were employed to examine the distribution and expression of HO-1 proteins in intestinal mucosa.
Results: MOJ jaundiced patients presented high levels of intestinal oxidative stress with a significantly increased level of lipid peroxidation [(1.79 +/- 0.24) vs (1.09 +/- 0.28) vs (1.18 +/- 0.32) nmol x mg(-1) x prot(-1), P = 0.041] and a decreased SOD activity [(303 +/- 10) vs (398 +/- 11) vs (406 +/- 11) nmol x mg(-1) x prot(-1), P = 0.017]. The apoptotic rate of intestinal epithelial cells was significantly higher in jaundiced group than in non-jaundiced control group. Apoptotic index was (69.1 +/- 5.9)%, (28.6 +/- 3.5)% and (10.2 +/- 2.5)% respectively (P < 0.01). The staining of HO-1 was predominantly localized in cytoplasm. In jaundiced patients, HO-1 was obviously elevated than those in the control group (HO-1 optical density 0.28 +/- 0.04 vs 0.20 +/- 0.04 vs 0.13 +/- 0.05) (P < 0.01). Similar outcomes were obtained by quantitative analysis of Western blotting images [HO-1/GAPDH (10.7 +/- 0.7)% vs (7.6 +/- 0.5)% vs (3.9 +/- 0.4)%, P < 0.01].
Conclusion: MOJ induces intestinal oxidative stress and it may be a key contributing factor to intestinal barrier failure in the patient population. HO-1 protein level is rising with the progression of obstruction. Perhaps HO-1 has a protective effect upon MOJ through anti-oxidative damage.