Effects Of Inducible Nitric Oxide Synthase And Protein Kinase C On Delayed Cardioprotection Induced By Preconditioning With Monophosphoryl Lipid A

Objective: To observe the delayed protection against ischemia-reperfusion (I/R) injury induced by preconditioning with monophosphoryl lipid A(MLA) in conscious rabbits, so as to explore effects of protein kinase C(PKC) and inducible nitric oxide synthase(iNOS) on MLA-induced cardioprotection.Method: 24 Newsland rabbits were randomly divided into 3 groups:[(1) control group saline was injected 24h before I/R, (2) experiment group MLA was injected 24h before I/R,(3) interference group MLA and PKC inhibitor/ Polymyxin B(PMB) were injected 24h and 30-minute before I/R respectively. All 3 groups underwent 30-minute ischemia following 60-minute reperfusion.The effects of MLA pretreatment on creatine kinase(CK) release, arrhythmia happening and the expression of iNOS were measured.Results: Experiment group and interference group both increased the iNOS expression, reduced the CK release and arrhythmia happening significantly compared with control group (all P<0.01)while these parameters besides iNOS expression were higher in interference group than in experiment group (difference of CK is significant,P<0.01;but difference of arrhythmia happening is insignificant,p>0.05 ), and iNOS expression in interference group is decreased comparing with experiment group although the difference is insignificant(P>0.05).There is no significant difference of iNOS expression between ischemic region and non-ischemic region(P>0.05).Conclusions: MLA pretreatment obviously attenuated I/R injury 24h later, i.e.,it can induce delayed protection. The delayed protection induced by MLA is mediated by iNOS and PKC may be involved in the cardioprotective effects through influence on iNOS expression.