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衣康酸在心肌缺血再灌注损伤中的动态变化及其作用研究

Dynamic changes and effects of itaconate in myocardial ischemia-reperfusion injury
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摘要 目的探究衣康酸在心肌缺血再灌注损伤(MI/RI)的动态变化及其作用。方法构建小鼠MI/RI模型,检测心脏组织及血浆中衣康酸的含量变化;通过腹腔注射补充外源性衣康酸后比较小鼠MI/RI后心功能变化;在体外构建H9C2细胞缺氧/复氧(H/R)模型,通过细胞计数试剂(CCK-8)、乳酸脱氢酶释放量以及原位末端标记法染色等对细胞损伤及凋亡情况进行评估。结果与假手术(Sham)组相比较,MI/RI后衣康酸在心脏组织中的表达呈上升趋势,且24 h比6 h升高更显著(P<0.001);而血浆表达在6 h时显著升高(P<0.0001),而后呈下降趋势,MI/RI后24 h显著降低(P<0.05),但仍显著高于Sham组(P<0.01);衣康酸处理显著减轻C57BL/6小鼠MI/RI后心功能障碍;与单纯的H/R组相比较,衣康酸处理显著提高细胞活力,改善H/R诱导的损伤,减少细胞凋亡。结论衣康酸在MI/RI后的心脏组织中持续升高,而在血浆中先升高后下降;外源性衣康酸改善小鼠MI/RI后心功能障碍,对H9C2细胞H/R损伤起保护作用,有望成为MI/RI重要干预手段。 Objective To explore the dynamics changes and effects of itaconate in myocardial ischemia-reperfusion injury(MIRI)in mice.Methods The MIRI model was constructed to detect changes in the content of itaconate in cardiac tissues and plasma.Comparison of changes in cardiac function after MIRI in mice with exogenous itaconate by intraperitoneal injection were conducted.The cell viability was assessed by the cell counting reagent(CCK-8),and cell damage was evaluated by the detection of lactate dehydrogenase(LDH)content in the hypoxia/reoxygenation(H/R)model for H9C2 cells in vitro.Results Compared with the sham surgery(Sham)group,the expression of itaconate in cardiac tissues after I/R showed an increasing trend and was more significantly elevated at 24h than that at 6h(P<0.001)whereas the plasma expression was significantly elevated at 6h(P<0.0001)and then showed a decreasing trend,and was significantly lower at 24h after I/R(P<0.05),but still significantly higher than that in the Sham group(P<0.01).Itaconate-treated significantly attenuated cardiac dysfunction after MIRI in C57BL/6 mice compared with the H/R group alone,itaconate significantly increased cell viability and improved hypoxia/reoxygenationinduced injury.Conclusion Itaconate is consistently elevated in cardiac tissue after I/R,whereas it increases and then decreases in plasma.Exogenous itaconate can improve the cardiac dysfunction after MIRI in mice and protect against hypoxia/reoxygenation injury in H9C2 cells.
作者 山文菊 崔君 蹇玉红 封林奇 易蔚 孙阳 Shan Wenju;Cui Jun;Jian Yuhong;Feng Linqi;Yi Wei;Sun Yang(Department of General Medical of The First Affiliate Hospital,Air Force Military Medical University,Shaanxi Xi’an 710032,China)
出处 《中国体外循环杂志》 2024年第2期139-144,共6页 Chinese Journal of Extracorporeal Circulation
基金 国家自然科学基金面上项目(81870266)。
关键词 衣康酸 心肌缺血再灌注损伤 缺氧/复氧 Itaconate Myocardial ischemia-reperfusion injury Hypoxia/reoxygenation
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