柠康酸对小鼠心肌缺血再灌注损伤的保护作用研究  

Study on the protective effect of citraconate on myocardial ischemia-reperfusion injury in mice

作　　者：封林奇 陈城 山文菊 蹇玉红 易蔚 Feng Linqi;Chen Cheng;Shan Wenju;Jian Yuhong;Yi Wei(Department of Cardiovascular Surgery,the First Affiliated Hospital of the Air Force Medical University,Shaanxi Xi’an 710032,China)

机构地区：[1]空军军医大学第一附属医院心血管外科,西安710032 [2]空军军医大学第一附属医院老年医学科,西安710032

出　　处：《中国体外循环杂志》2025年第2期162-169,共8页Chinese Journal of Extracorporeal Circulation

基　　金：陕西省重点研发计划(2023-ZDLSF-39)。

摘　　要：目的探讨柠康酸在脂多糖(LPS)/干扰素-γ(IFN-γ)诱导RAW264.7巨噬细胞在炎症中的作用以及在小鼠心肌缺血再灌注损伤(MI/RI)中的作用。方法通过LPS/IFN-γ诱导RAW264.7巨噬细胞产生炎症反应,细胞计数试剂(CCK-8)评估柠康酸处理后细胞活力,实时荧光定量聚合酶链反应和蛋白免疫印迹评价RAW264.7巨噬细胞的炎症反应;通过构建MI/RI模型,比较小鼠腹腔注射外源性柠康酸后的心功能变化。通过荧光免疫染色、实时荧光定量聚合酶链反应和蛋白免疫印迹测定MI/RI后心脏的炎症反应,通过Bax蛋白表达和原位末端标记法染色测定MI/RI后心肌细胞凋亡。结果柠康酸在给药剂量1~10 mmol/L和处理时间4 h时可显著减轻LPS/IFN-γ诱导的RAW264.7巨噬细胞的炎症,并且具有剂量依赖性。柠康酸治疗显著减轻了小鼠MI/RI后的心脏炎症和心肌细胞凋亡,显著改善了小鼠MI/RI后的心功能。结论柠康酸通过减轻小鼠MI/RI后的心脏炎症和心肌细胞凋亡,改善了小鼠MI/RI后的心脏功能。Objective To investigate the role of citraconate in LPS/IFN-γinduced inflammation of RAW264.7 macrophages and its effect on myocardial ischemia-reperfusion injury(MI/RI)in mice.Methods The inflammatory response of RAW264.7 macrophages was induced by LPS/IFN-γ,and the cell viability after citraconate treatment was evaluated by cell counting reagent(CCK-8).The inflammatory response of RAW264.7 macrophages was evaluated by real-time fluorescence quantitative PCR and western blot.The MI/RI model was constructed to compare the changes in cardiac function after intraperitoneal injection of exogenous citraconate in mice.The inflammatory response of the heart after MI/RI was determined by fluorescence immunostaining,real-time fluorescence quantitative PCR,and protein immunoblotting.The expression of BAX(Bcl-2 associated X)protein and apoptosis of myocardial cells after MI/RI were measured by Tunel.Results The dosage and treatment time of citraconate for LPS/IFN-γ-induced RAW264.7 macrophages were determined to be 1 mmol/L to 10 mmol/L for 4 hours;citraconate significantly alleviated LPS/IFN-γinduced inflammation in RAW264.7 macrophages and exhibited a dose-dependent effect.Citraconate treatment significantly reduced cardiac inflammation and myocardial cell apoptosis in mice after MI/RI,and significantly improved cardiac function in mice after MI/RI.Conclusion Citraconate improves the cardiac function of mice after MI/RI by alleviating cardiac inflammation and myocardial cell apoptosis.

关 键 词：柠康酸 心肌缺血-再灌注损伤 RAW264.7巨噬细胞 心脏功能 炎症反应 心肌细胞凋亡 

分 类 号：R285.5[医药卫生—中药学]