Effects of cardiopulmonary bypass on tight junction protein expressions in intestinal mucosa of rats

World J Gastroenterol. 2008 Oct 14;14(38):5868-75. doi: 10.3748/wjg.14.5868.

Abstract

Aim: To investigate the tight junction protein expressions of intestinal mucosa in an experimental model of cardiopulmonary bypass (CPB) in rats.

Methods: Thirty anesthetized rats were randomly divided into two groups: Group S (n = 10) served as sham operation and group C (n = 20) served as CPB which underwent CPB for 1 h. Expression of occludin and zonula occludens-1 (ZO-1) were determined by Western blotting and immunotochemistry, respectively. Plasma levels of diamine oxidase (DAO) and d-lactate were determined using an enzymatic spectrophotometry.

Results: Immunohistochemical localization of occludin and ZO-1 showed disruption of the tight junctions in enterocytes lining villi at the end of CPB and 2 h after CPB. The intensities of the occludin and ZO-1 at the end of CPB were lower than those of control group (76.4% +/- 22.5% vs 96.5% +/- 28.5% and 62.4% +/- 10.1% vs 85.5% +/- 25.6%, P < 0.05) and were further lower at 2 h after CPB (50.5% +/- 10.5% and 45.3% +/- 9.5%, P < 0.05). Plasma d-lactate and DAO levels increased significantly (8.688 +/- 0.704 vs 5.745 +/- 0.364 and 0.898 +/- 0.062 vs 0.562 +/- 0.035, P < 0.05) at the end of CPB compared with control group and were significantly higher at 2 h after CPB than those at the end of CPB (9.377 +/- 0.769 and 1.038 +/- 0.252, P < 0.05). There were significant negative correlations between occludin or ZO-1 expression and DAO (r(2) = 0.5629, r(2) = 0.5424, P < 0.05) or d-lactate levels (r(2) = 0.6512, r(2) = 0.7073, P < 0.05) both at the end of CPB and 2 h after CPB.

Conclusion: CPB markedly down-regulates the expression of occludin and ZO-1 proteins in intestinal mucosa of rats. The close correlation between expression of tight junctions (TJs) and plasma levels of DAO or d-lactate supports the hypothesis that intestinal permeability increases during and after CPB because of decreases in the expressions of TJs.

MeSH terms

  • Amine Oxidase (Copper-Containing) / blood
  • Animals
  • Blotting, Western
  • Cardiopulmonary Bypass / adverse effects*
  • Down-Regulation
  • Enterocytes / metabolism*
  • Enterocytes / ultrastructure
  • Ileum / metabolism*
  • Ileum / ultrastructure
  • Immunohistochemistry
  • Lactic Acid / blood
  • Male
  • Membrane Proteins / metabolism*
  • Microvilli / metabolism
  • Models, Animal
  • Occludin
  • Permeability
  • Phosphoproteins / metabolism*
  • Rats
  • Rats, Wistar
  • Tight Junctions / metabolism*
  • Tight Junctions / ultrastructure
  • Time Factors
  • Zonula Occludens-1 Protein

Substances

  • Membrane Proteins
  • Occludin
  • Ocln protein, rat
  • Phosphoproteins
  • Tjp1 protein, rat
  • Zonula Occludens-1 Protein
  • Lactic Acid
  • Amine Oxidase (Copper-Containing)