PLASMA LEVELS OF LIVER-SPECIFIC MIR-122 IS MASSIVELY INCREASED IN A PORCINE CARDIOGENIC SHOCK MODEL AND ATTENUATED BY HYPOTHERMIA
PLASMA LEVELS OF LIVER-SPECIFIC MIR-122 IS MASSIVELY INCREASED IN A PORCINE CARDIOGENIC SHOCK MODEL AND ATTENUATED BY HYPOTHERMIA
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DOI：
10.1097/shk.0b013e31823f1811
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发表时间：
2012-02-01
期刊：
影响因子：
3.1
通讯作者：
Erlinge, David
中科院分区：
文献类型：
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作者：
Andersson, Patrik;Gidlof, Olof;Erlinge, David
器官损伤后，组织特异性循环 micro-RNA (miRNA) 被释放到血液中。在缺血性猪心源性休克模型中，我们研究了心脏特异性 miR-208b 和肝脏特异性 miR-122 的释放模式，并评估了治疗性低温对其各自血浆水平的影响。将猪麻醉，通过将经皮冠状动脉介入球囊在左前降支近端充气40分钟，然后再灌注，诱导心源性休克。满足预定的休克标准后，猪被随机分配至低温（33 摄氏度，n = 6）或常温（38 摄氏度，n = 6）。从血浆中提取循环 miRNA，并通过定量实时聚合酶链反应 (PCR) 进行测量。通过从猪组织中提取 miRNA，然后进行定量实时 PCR 来评估组织特异性。在体外，通过实时 PCR 评估暴露于缺氧或酸中毒的培养肝细胞系中 miR-122 的释放。 miR-122被发现具有高度肝脏特异性，而miR-208b仅在心脏中表达。在对照组中，缺血性心源性休克导致血浆中 miR-122 (P < 0.05) 和 miR-208b (P < 0.05) 水平分别增加 460,000 倍和 63,000 倍。与常温组相比，低温治疗显着减少了 miR-122 的增加（P < 0.005）。在我们的模型中，低温是在冠状动脉再灌注后开始的，并且不会影响之前通过磁共振成像评估的心肌损伤或 miR-208b 的血浆水平。我们的结果表明，在心源性休克的情况下，肝脏特异性 miR-122 被释放到循环中，并且治疗性低温显着降低了 miR-122 的水平。
Tissue-specific circulating micro-RNAs (miRNAs) are released into the blood after organ injury. In an ischemic porcine cardiogenic shock model, we investigated the release pattern of cardiac-specific miR-208b and liver-specific miR-122 and assessed the effect of therapeutic hypothermia on their respective plasma levels. Pigs were anesthetized, and cardiogenic shock was induced by inflation of a percutaneous coronary intervention balloon in the proximal left anterior descending artery for 40 min followed by reperfusion. After fulfillment of the predefined shock criteria, the pigs were randomized to hypothermia (33 degrees C, n = 6) or normothermia (38 degrees C, n = 6). Circulating miRNAs were extracted from plasma and measured with quantitative real-time polymerase chain reaction (PCR). Tissue specificity was assessed by miRNA extraction from porcine tissues followed by quantitative real-time PCR. In vitro, the release of miR-122 from a cultured hepatocyte cell line exposed to either hypoxia or acidosis was assessed by real-time PCR. miR-122 was found to be highly liver specific, whereas miR-208b was expressed exclusively in the heart. In the control group, ischemic cardiogenic shock induced a 460,000-fold and a 63,000-fold increase in plasma levels of miR-122 (P < 0.05) and miR-208b (P < 0.05), respectively. Therapeutic hypothermia significantly diminished the increase in miR-122 compared with the normothermic group (P < 0.005). In our model, hypothermia was initiated after coronary reperfusion and did not affect either myocardial damage as previously assessed by magnetic resonance imaging or the plasma level of miR-208b. Our results indicate that liver-specific miR-122 is released into the circulation in the setting of cardiogenic shock and that therapeutic hypothermia significantly reduces the levels of miR-122.