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首页> 外文期刊>American Journal of Physiology >Macrophage migration inhibitory factor is a cardiac-derived myocardial depressant factor.
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Macrophage migration inhibitory factor is a cardiac-derived myocardial depressant factor.

机译：巨噬细胞迁移抑制因子是心脏衍生的心肌抑制因子。

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Macrophage migration inhibitory factor (MIF) is a pluripotent proinflammatory cytokine that is ubiquitously expressed in organs, including the heart. However, no specific role for MIF in modulating cardiac performance has yet been described. Therefore, we examined cardiac MIF expression in mice after LPS challenge (4 mg/kg) and tested the hypothesis that MIF is a mediator of LPS-induced cardiac dysfunction. Western blots of whole heart lysates, as well as immunohistochemistry, documented constitutive MIF protein expression in the heart. Cardiac MIF protein levels significantly decreased after LPS challenge, reaching a nadir at 12 h, and then returned to baseline by 24 h. This pattern was consistent with MIF release from cytoplasmic stores after endotoxin challenge. After release of protein, MIF mRNA levels increased 24-48 h postchallenge. To determine the functional consequences of MIF release, we treated LPS-challenged mice with anti-MIF neutralizing antibodies or isotype control antibodies. Anti-MIF-treated animals had significantly improved cardiac function, as evidenced by a significant improvement in left ventricular (LV) fractional shortening percentage at 8, 12, 24, and 48 h after endotoxin challenge. In support of these findings, perfusion of isolated beating mouse hearts (Langendorff preparation) with recombinant MIF (20 ng/ml) led to a significant decrease in both systolic and diastolic performance [LV pressure (LVP), positive and negative first derivative of LVP with respect to time, and rate of LVP rise at developed pressure of 40 mmHg]. This study demonstrates that MIF mediates LPS-induced cardiac dysfunction and suggests that MIF should be considered a pharmacological target for the treatment of cardiac dysfunction in sepsis and potentially other cardiac diseases.
机译：巨噬细胞迁移抑制因子（MIF）是一种多能促炎细胞因子，在包括心脏在内的器官中普遍表达。但是，尚未描述MIF在调节心脏功能方面的特定作用。因此，我们检查了LPS攻击（4 mg / kg）后小鼠心脏MIF的表达，并检验了MIF是LPS诱导的心脏功能障碍的介质的假说。整个心脏溶解产物的Western印迹以及免疫组织化学证明了心脏中本构性MIF蛋白的表达。 LPS攻击后，心脏MIF蛋白水平显着降低，在12 h达到最低点，然后在24 h恢复至基线。这种模式与内毒素攻击后从细胞质存储中释放的MIF一致。释放蛋白质后，攻击后24-48小时MIF mRNA水平升高。为了确定MIF释放的功能后果，我们用抗MIF中和抗体或同型对照抗体处理了LPS攻击的小鼠。抗MIF处理的动物的心脏功能显着改善，内毒素激发后第8、12、24和48小时左心室（LV）分数缩短百分比显着改善。为了支持这些发现，用重组MIF（20 ng / ml）灌注离体的跳动小鼠心脏（Langendorff制剂）会导致收缩压和舒张压[LV压力（LVP），LVP的正负一阶导数]显着降低。在时间上，在40 mmHg的开发压力下LVP的上升速率]。这项研究表明，MIF介导LPS引起的心脏功能障碍，并建议将MIF视为治疗败血症和其他潜在心脏病的心脏功能障碍的药理学靶标。

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