Effects of heme oxygenase-1 protein transduction on intestinal injury in septic rats

Objective To investigate the effects of heme oxygenase-1 (HO-1) protein transduction mediated by cell penetrating peptide PEP-1 on intestinal injury in a rat model of sepsis induced by cecal ligation and puncture (CLP).Methods Twenty-four healthy male Sprague-Dawley rats,aged 7-9 weeks,weighing 210-260 g,were randomly divided into 4 groups (n =6 each) using a random number table:sham operation group (group S),group CLP,low-dose fusion protein PEP-1-HO-1 + CLP group (group P1) and high-dose fusion protein PEP-1-HO-1 + CLP group (group P2).Fusion protein PEP-1-HO-1 0.3 mg was administrated via the left iliac vein at 1 h before CLP and 5 h after CLP in group P1.Fusion protein PEP-1-HO-1 0.6 mg was administrated via the left iliac vein at 1 h before CLP and 5 h after CLP in group P2.The equal volume of normal saline was given instead of PEP-1-HO-1 in the other groups.The animals underwent laparotomy,but the caecum was not ligated or punctured in group S.Blood samples were collected at 12 h after CLP from the right common carotid artery for measurement of serum TNF-α and IL-6 levels.The rats were then sacrificed and intestines were removed for microscopic examination and for determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in intestinal tissues.Results Compared with group S,the serum TNF-α and IL-6 levels,and MDA content in intestinal tissues were significantly increased,while SOD activity in intestinal tissues was decreased in CLP,P1 and P2 groups.Compared with group CLP,the serum TNF-α and IL-6 levels,and MDA content in intestinal were significantly decreased,while SOD activity in intestinal tissues was increased in P1 and P2 groups.Compared with group P1,the serum TNF-α and IL-6 levels,and MDA content in intestinal tissues were significantly decreased,while SOD activity in intestinal tissues was increased in group P2.The pathological changes of intestines were significantly mitigated in P1 and P2 groups as compared with group CLP.Conclusion HO-1 protein transduction attenuates intestinal injury induced by sepsis in rats,and the mechanism is related to inhibition of systemic inflammatory responses and lipid peroxidation in intestinal tissues. Key words: Heme oxygenase-1 ;  Recombinant fusion proteins;  Transduction, genetic;  Sepsis; Intestines