衰老心肌缺血/再灌注损伤增加的新机制—程序性坏死的关键作用 |
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引用本文: | 李 晨,陈 迈,马 恒. 衰老心肌缺血/再灌注损伤增加的新机制—程序性坏死的关键作用[J]. 心脏杂志, 2016, 28(3): 263-267 |
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作者姓名: | 李 晨 陈 迈 马 恒 |
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作者单位: | (第四军医大学:1.基础医学院病理生理学教研室,2.西京医院心血管内科,3.基础医学院生理学教研室,陕西 西安 710032) |
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基金项目: | 国家优秀青年科学基金项目资助(81322004) 国家自然科学基金项目资助(81170108,81470410) |
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摘 要: | 目的 探讨程序性坏死(necroptosis)在衰老心肌缺血/再灌注(I/R)损伤中的关键作用。 方法 成年( 3~4月龄)和老龄( 22~24月龄)雄性C57BL/6小鼠20只各随机分为对照组与I/R组,建立小鼠急性心肌I/R模型(缺血30 min再灌注4 h)。再灌注结束后,取心肌组织并分别应用蛋白质免疫印迹法(Western blot)和免疫共沉淀法(Co-Immunoprecipitation;Co-IP)检测necroptosis标志蛋白的表达及其修饰变化。结果 与成年心肌相比,necroptosis的标志蛋白RIP1、RIP3在衰老心肌中的表达均升高(P<0.05),necroptosis的调节蛋白去乙酰化酶SIRT2的表达及活性也显著升高(P<0.05),RIP1的去乙酰化水平显著升高(P<0.05)。给予小剂量necroptosis抑制剂Necrostatin-1(Nec-1)处理,可以显著减少衰老心肌I/R梗死面积(P<0.05)。结论 本研究发现在衰老心肌I/R损伤中necroptosis显著增加,表明necroptosis可能在衰老心肌缺血损伤中有重要作用。
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关 键 词: | 衰老 程序性坏死 心肌缺血/再灌注 |
收稿时间: | 2015-11-04 |
Supplemental mechanism of increased reperfusion injury in senescent myocardial ischemia: significant role of necroptosis |
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Abstract: | AIM Research shows that aging hearts have less tolerance to myocardial ischemia reperfusion (I/R) injury and this leads to the design of investigating the role of necroptosis in senescent myocardial I/R injury. METHODS Male C57BL/6 mice aged 22-24 months were randomized into I/R group and vehicle control group. Adult male (3-4 months) C57BL/6 mice served as control group. The left anterior descending artery was ligated for 30 min followed by 4 h reperfusion to establish the acute myocardial I/R mouse model. Myocardial tissue was obtained after reperfusion. Western blot was used to detect necroptosis-related protein expression. Co-immunoprecipitation was used to detect the modification of the necroptosis-related protein. RESULTS Necroptosis was commonly increased in hearts of aged mice (P<0.05). The expression of necroptosis biomarker, RIP1 and RIP3, is increased (P<0.05). Expression and activity of the regulator protein deacetylase SIRT2 increased as well as the deacetylation of RIP1 (P<0.05). Meanwhile, inhibiting necroptosis by using the inhibitor necrostatin-1 (Nec-1) reduced the infarct size in aged hearts (P<0.05). CONCLUSIONN ecroptosis displays an increased expression in aged myocardial I/R injury, indicating the important role necroptosis plays in age-related myocardial ischemia injury. |
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