Effects Of Low-dose Ketamine Preconditioning On Heme-Oxygenase-1 Expression During Intestinal Ischemia/reperfusion Injury In Rats

Objective:To investigate the protective effect of ketamine on intestinal mucosa in rats with intestinal ischemia/reperfusion and the mechanism related to heme-oxygenase-1 protein expression.Methods:48 male rats were randomly divided into 6 groups:group A(KTM 10mg/kg i.p given 30 min before Shame);group B(Saline 0.2ml i.p given 30 min before Shame);group C(KTM 10mg/kg i.p given 30 min before I/R);group D(Saline 0.2ml i.p given 30 min before I/R);group E(ZnPPⅨ5mg/kg,KTM10mg/kg i.p given 30 min before I/R)group F(ZnPPⅨ5mg/kg,Saline 0.2ml i.p given 30 min before I/R),n=8 in each group.The rat model of intestinal I/R injury was reproduced by occluding the superior mesenteric artery of the rats for 1 hour and subsequent reperfusion was for 6 hour.Intestine tissues were gathered for MDA and SOD determination at various intervals.Expression and distributions of HO-1 and iNOS in intestine tissue were detected by inmunohistochemistry and morphometry computer image analysis.Intestinal pathology was scored by Chius score system under light microscope.Result:1 There show no significant differences between groupA and groupB in all results.(P＞0.05)2 Compared with groupB,the content of MDA were obviously higher in all I/R groups(P＜0.01 or P＜0.05);Compared with groupC the content of MDA were obviously higher in groupD,groupE and groupF(P＜0.05);and there were no significant differences among groupD,groupE and groupF. 3 Compared with groupB,the activity of SOD was lower in I/R groupD,groupE and groupF(P＜0.01),whereas there were no significant differences than that in groupC;Compared with groupC the activity of SOD was lower in I/R groupD,groupE and groupF(P＜0.05);there were no significant differences among groupD,groupE and groupF.4 Compared with groupB,the Chius score in all I/R groups were obviously higher(P＜0.01 or P＜0.05);compared with groupD,the Chius score were significantly attenuated by ketamine in groupC(P＜0.01)and were reversed by Znic protoporphorinⅨin groupE(P＜0.05).5 Compared with groupB,expressions of HO-1 were markedly increased in all I/R groups(P＜0.01);Compared with groupD,expression of HO-1 was obviously higher in groupC(P＜0.05);Compared with groupC,expression of HO-1 was significantly lower in groupE(P＜0.05).6 Compared with groupB,expressions of iNOS were markedly increased in all I/R groups(P＜0.01or P＜0.05);Compared with groupD,expression of iNOS was obviously lower in groupC(P＜0.05);Compared with groupC,expression of iNOS was significantly higher in groupE(P＜0.05).Conclusion:Low-dose ketamine inhibits intestinal mucosa injury during intestinal ischemia/reperfusion,this protective effect may be partly though induction of HO-1 and though down-regulatiion of iNOS.