羟基酪醇对脓毒症诱导的急性心肺损伤的保护作用及机制

Mechanism of hydroxytyrosol alleviates sepsis-induced acute lung injury and cardiovascular dysfunction

目的:探究羟基酪醇(HYD)对脓毒症诱导的急性心肺损伤的保护作用及机制。方法:盲肠结扎穿孔术构建小鼠脓毒症模型,HYD 20 mg/kg灌胃治疗。检测左心室收缩功能、心脏炎症因子mRNA和肺泡灌洗液炎症因子水平、肺损伤和中粒浸润程度、心肺组织SIRT1和NF-κB水平、小鼠7 d生存率。结果:HYD升高左心室射血分数(EF)和左心室短轴缩短率(FS)(P<0.05),降低心脏和肺泡灌洗液炎症因子水平(P<0.01);改善肺损伤,减轻中性粒细胞浸润(P<0.01),延长生存率(P<0.01),HYD上调心肺组织SIRT1表达,抑制NF-κB通路活化。结论:HYD通过上调SIRT1和抑制NF-κB炎症信号通路而减轻脓毒症诱导的急性心肺损伤。

Objective: To explore the mechanism of hydroxytyrosol protecting sepsis-induced acute lung injury and cardiovascular dysfunction. Methods: Polymicrobial sepsis was induced in mice by cecal ligation and puncture.Mice were intragastric administered hydroxytyrosol(20 mg/kg).Then we assessed the cardiac function,the levels of inflammatory cytokine in myocardium and pulmonary tissues,the pulmonary tissue damage,the neutrophil/leukocyte infiltration,the levels of inflammatory cytokine in bronchoalveolar lavage fluid,the SIRT1 expression and the phosphorylation of the NF-κB in myocardium and pulmonary tissues,and observed 7-days survival rate. Results: Hydroxytyrosol treatment improved left ventricular systolic function,higher value of EF(left ventricular ejection fractions)and FS(fractional shortening)( P <0.05),and decreased the expression of inflammatory mediators in myocardium tissue( P <0.01).Hydroxytyrosol treatment obviously alleviate the pulmonary tissue damages and decrease neutrophil/leukocyte infiltration and the expression of inflammatory mediators( P <0.01).Hydroxytyrosol treatment up regulated SIRT1 expression and inhibited the phosphorylation of the NF-κB both in pulmonary and myocardium tissues.In addition,hydroxytyrosol could significantly improve the survival rate of sepsis mice( P <0.01). Conclusion: Hydroxytyrosol could alleviate sepsis-induced acute lung injury and cardiac dysfunction by activating the SIRT1 signaling pathway,with suppressing NF-κB-mediated inflammatory signaling.