The?cardioprotection?induced?by?lipopolysaccharide?involves?phos-phoinositide?3-kinase/Akt?and?high?mobility?group?box?1?pathways

Objective:?The?mechanisms?by?which?lipopolysaccharide?(LPS)?pretreatment?induces?cardioprotection?fol-lowing?ischaemia/reperfusion?(I/R)?have?not?been?fully?elucidated.?We?hypothesized?that?activation?of?phosph-oinositide?3-kinase?(PI3K)/Akt?and?high?mobility?group?box?1?(HMGBx1)?signaling?plays?an?important?role?in?LPS-induced?cardioprotection.?Methods:?In?in?vivo?experiments,?age-?and?weight-?matched?male?C57BL/10Sc?wild?type?mice?were?pretreated?with?LPS?before?ligation?of?the?left?anterior?descending?coronary?followed?by?reperfusion.?Infarction?size?was?examined?by?triphenyltetrazolium?chloride?(TTC)?staining.?Akt,?phospho-Akt,?and?HMGBx1?were?assessed?by?immunoblotting?with?appropriate?primary?antibodies.?In?situ?cardiac?myocyte?apop-tosis?was?examined?by?the?TdT-mediated?dUTP?nick-end?labeling?(TUNEL)?assay.?In?an?in?vitro?study,?rat?cardiac?myoblasts?(H9c2)?were?subdivided?into?two?groups,?and?only?one?was?pretreated?with?LPS.?After?pretreatment,?the?cells?were?transferred?into?a?hypoxic?chamber?under?0.5%?O2.?Levels?of?HMGBx1?were?assessed?by?immuno-blot.?Results:?In?the?in?vivo?experiment,?pretreatment?with?LPS?reduced?the?at?risk?infarct?size?by?70.6%?and?the?left?ventricle?infarct?size?by?64.93%?respectively.?Pretreatment?with?LPS?also?reduced?cardiac?myocytes?apoptosis?by?39.1%?after?ischemia?and?reperfusion.?The?mechanisms?of?LPS?induced?cardioprotection?involved?increasing?PI3K/Akt?activity?and?decreasing?expression?of?HMGBx1.?In?the?in?vitro?study,?pretreatment?with?LPS?reduced?the?level?of?HMGBx1?in?H9c2?cell?cytoplasm?following?hypoxia.?Conclusion:?The?results?suggest?that?the?car-dioprotection?following?I/R?induced?by?LPS?pretreatment?involves?PI3K/Akt?and?HMGBx1?pathways.