β1 receptor blocker decreases the myocardial inflammation in the sepsis adult rats through inhibition of TLR4/NF-κB signaling pathway / 中华危重病急救医学

ABSTRACT

Objective? To?explore?whether?β1?receptor?blocker?could?decrease?the?myocardial?inflammation??through?the?Toll-like?receptor?4/nuclear?factor-κB?(TLR4/NF-κB)?signaling?pathway?in?the?sepsis?adult?rats.? Methods? ?Sixty?male?Wistar?rats?(250-300?g)?aged?3?months?old?were?allocated?to?four?groups?by?random?number?table?(n?=?15)?sham?operation?group?(S?group),?sepsis?model?group?(CLP?group),?β1?receptor?blocker?esmolol?intervention?group??(ES?group),?and?inhibitor?of?the?TLR4?E5564?intervention?group?(E5564?group).?The?rat?sepsis?model?was?established?by?cecal?ligation?and?puncture?(CLP);?S?group?of?rats?underwent?only?an?incision.?Rats?in?S?group,?CLP?group?and?E5564?group?were?subcutaneous?injected?with?0.9%?sodium?chloride?(NaCl)?2.0?mL/kg.?Besides,?the?rats?in?ES?group?were?injected?with?esmolol?(15?mg·kg-1·h-1)?by?micro?pump?through?the?caudal?vein.?The?rats?in?E5564?group?were?injected?with?E5564?(0.3?mg·kg-1·h-1)?by?micro?pump?through?the?caudal?vein?1?hour?before?the?CLP?surgery.?Samples?were?collected?6?hours?after?the?modelling?in?each?group.?The?average?arterial?pressure?(MAP)?and?cardiac?output?index?(CI)?were?monitored?by?PU?electrical?conduction?ECG?monitor.?The?levels?of?serum?cardiac?troponin?I?(cTnI),?interleukin-1β?? (IL-1β)?and?tumor?necrosis?factor-α(TNF-α)?were?detected?by?enzyme?linked?immunosorbent?assay?(ELISA).?The?expressions?of?TLR4,?NF-κB?p65,?IL-1β,?TNF-α?in?myocardial?tissue?was?detected?by?Western?Blot.? Results? There?was?no?significant?difference?in?MAP?in?each?group.?Compared?with?the?S?group,?the?CI?in?the?CLP?group?was?significantly?decreased,?the?levels?of?serum?cTnI,?IL-1β,?TNF-α?were?significantly?increased,?the?protein?expressions?of?myocardial?tissue?TLR4,?NF-κB?p65,?IL-1β?and?TNF-α?were?significantly?increased.?Compared?with?the?CLP?group,?the?CI?in?the?ES?group?and?E5564?group?were?significantly?increased?(mL·s-1·m-2?58.6±4.3,?58.9±4.4?vs.?41.2±3.9,?both?P?<?0.01),?the?levels?of?serum?cTnI,?IL-1β?and?TNF-α?were?significantly?decreased?[cTnI?(μg/L)?1?113.81±26.64,?1?115.74±25.90?vs.?1?975.96±42.74;?IL-1β(ng/L)?39.6±4.3,?38.9±4.4?vs.?61.2±3.9;?TNF-α?(ng/L)?43.1±2.8,?48.7±2.6?vs.?81.3±4.4,?all?P?<?0.01],?the?protein?expressions?of?myocardial?tissue?NF-κB?p65,?IL-1β,??TNF-αwere?significantly?decreased?(NF-κB?p65/β-actin?0.31±0.03,?0.43±0.04?vs.?0.85±0.08;?IL-1β/β-actin?0.28±0.05,?0.32±0.03?vs.?0.71±0.06;?TNF-α/β-actin?0.18±0.04,?0.28±0.03?vs.?0.78±0.07,?all?P?<?0.01),?but?there?was?no?significant?difference?in?protein?expression?of?TLR4?(TLR4/β-actin?0.89±0.07,?0.87±0.09?vs.?0.95±0.09,?both?P?>?0.05).?There?was?no?significant?difference?in?CI,?the?levels?of?serum?cTnI,?IL-1β,?TNF-α,?and?the?protein?expressions?of?myocardial?tissue?TLR4,?NF-κB?p65,?IL-1β,?TNF-αbetween?ES?group?and?E5564?group?(all?P?>??0.05).? Conclusion? β1?receptor?blocker?esmolol?may?inhibit?myocardial?inflammatory?response?in?sepsis?adult?rats?through?TLR4/NF-κB?signaling?pathway,?thereby?alleviating?sepsis-induced?myocardial?injury.