摘要：
Objective? To?explore?whether?β1?receptor?blocker?could?decrease?the?myocardial?inflammation??through?the?Toll-like?receptor?4uclear?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??0.05).?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.%目的? 探讨β1受体阻滞剂是否通过Toll样受体4?/核转录因子-κB?(TLR4/NF-κB)信号通路抑制脓毒症大鼠心肌炎症反应.方法? 按随机数字表法将3月龄250～300?g清洁级雄性Wistar大鼠分配至假手术组(S组)、脓毒症模型组?(CLP组)、β1受体阻滞剂艾司洛尔干预组(ES组)、?TLR4受体拮抗剂干预组(E5564组),每组15只.采用盲肠结扎穿孔术(CLP)制备脓毒症动物模型;S组仅剖腹,不进行盲肠结扎、穿孔.S组、?CLP组、E5564?组关腹后皮下注射0.9%氯化钠(NaCl)2.0?mL/kg补液;除皮下补液外,ES组经尾静脉持续泵入艾司洛尔15?mg·kg-1·h-1,E5564?组于术前1?h经尾静脉持续泵入E5564?0.3?mg·kg-1·h-1.各组于制模后6?h采集标本,采用PU电传导心电监护仪监测平均动脉压(MAP)及心排血指数(CI),采用酶联免疫吸附试验(ELISA)检测血清心肌肌钙蛋白I(cTnI)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平,采用蛋白质免疫印迹试验(Western?Blot)检测心肌组织TLR4、?NF-κB?p65、IL-1β、TNF-α蛋白表达.结果? 各组大鼠MAP比较差异均无统计学意义.与S组相比,?CLP组CI明显降低,血清cTnI、IL-1β、TNF-α水平明显升高,心肌组织TLR4、NF-κB?p65、IL-1β、TNF-α蛋白表达水平明显上调.与CLP组比较,ES组和E5564组CI均明显升高(mL·s-1·m-2 :?58.6±4.3、58.9±4.4?比41.2±3.9,均P＜0.01),血清cTnI、IL-1β、TNF-α水平明显降低〔cTnI(μg/L):1?113.81±26.64、1?115.74±25.90比1?975.96±42.74,IL-1β(ng/L):?39.6±4.3、38.9±4.4比61.2±3.9,?TNF-α(ng/L):?43.1±2.8、48.7±2.6比81.3±4.4,均?P＜0.01〕,心肌组织NF-κB?p65、IL-1β、TNF-α蛋白表达水平显著下调(NF-κB?p65/β-actin:?0.31±0.03、0.43±0.04比0.85±0.08,?IL-1β/β-actin:?0.28±0.05、0.32±0.03比0.71±0.06,?TNF-α/β-actin :0.18±0.04、0.28±0.03比0.78±0.07,均P＜0.01),而TLR4蛋白表达水平差异无统计学意义(TLR4/β-actin :0.89±0.07、0.87±0.09比0.95±0.09,均P＞0.05).ES组与E5564组CI和血清cTnI、IL-1β、TNF-α水平以及心肌组织TLR4、NF-κB?p65、IL-1β、TNF-α蛋白表达水平比较差异均无统计学意义(均P＞0.05).结论? β1受体阻滞剂艾司洛尔可能通过TLR4/NF-κB?信号通路抑制脓毒症大鼠心肌炎症反应,从而减轻脓毒症心肌损伤.
