Sci Transl Med:辅酶Q10对低氧状态下心脏外科术中低温的心肌有保护作用

2019-04-27 文韬 中国循环杂志

4月24日,中国医学科学院阜外医院心外科张浩教授团队在《科学:转化医学》(Science Translational Medicine)发表了最新的研究成果,揭示了长期处于低氧状态的患者心脏外科体外循环术中低温治疗的心肌保护效果不良的可能原因,而补充辅酶Q10有是一种新的心肌保护策略。杂志为该论文同期配发题为“心肌保护:冷失其酷”(Cardioprotection loses its cool)的

4月24日,中国医学科学院阜外医院心外科张浩教授团队在《科学:转化医学》(Science Translational Medicine)发表了最新的研究成果,揭示了长期处于低氧状态的患者心脏外科体外循环术中低温治疗的心肌保护效果不良的可能原因,而补充辅酶Q10有是一种新的心肌保护策略。杂志为该论文同期配发题为“心肌保护:冷失其酷”(Cardioprotection loses its cool)的导读,认为张浩团队研究揭示了冷诱导RNA结合蛋白(CIRBP)在低温心肌保护中的作用,并提出针对低氧患者的个体化心肌保护策略,具有重要的转化医学意义。

紫绀型先天性心脏病、慢阻肺、睡眠呼吸暂停综合征患者以及高海拔地区的人群处于长期低氧状态,许多临床证据表明,这些患者心脏外科术后发生低心排综合征等相关并发症的风险较高,但机制仍不明确,而且缺乏个性化的心肌保护策略。

低温是体外循环下心脏直视手术中不可缺少的重要的心肌保护环节。但低温在降低心肌氧耗的同时,也不可避免带来寒冷刺激下的心肌损伤,而此时心肌细胞需同时表达一系列冷休克蛋白来拮抗冷刺激带来的副作用。

张浩研究团队通过建立模拟临床场景的大鼠体外模型,发现体外循环期间低温可以诱导心脏冷诱导CIRBP的表达,而抑制此蛋白表达则会导致心脏功能显着受损。该团队进一步通过转基因大鼠、心肌细胞培养等一系列研究发现,长期慢性低氧会诱导心肌细胞发生甲基化的表观遗传学改变,导致CIRBP表达下降,并且丧失对低温的反应性。低温下的CIRBP表达被抑制后,可导致体外循环期间心肌组织的泛醌合成障碍、辅酶Q10的合成锐减,最终削弱低温的心肌保护效果。

通过在心脏停博液中补充额外的辅酶Q10可弥补冷刺激后CIRBP下降带来的负面效应。

体外循环中低温诱导心肌辅酶Q10合成来拮抗低温带来的负面效应,但是这一过程被缺氧抑制

研究团队同期采集紫绀先心病和来自高海拔地区患者的心肌组织样本,验证了上述结论,为临床转化提供了证据。

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    2019-07-10 drwjr
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    2019-06-20 bsmagic9140
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