Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate.
Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate.
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高迁移率族box-1在心肌缺血/再灌注损伤中的作用及丙酮酸乙酯的作用
DOI：
10.3892/etm.2015.2290
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发表时间：
2015-04
影响因子：
2.7
通讯作者：
Fang J
中科院分区：
文献类型：
--
作者：
Lin Y;Chen L;Li W;Fang J
高迁移率族蛋白1（HMGB 1）是一种促炎细胞因子，在缺血/再灌注（I/R）后触发并放大炎症级联反应。丙酮酸乙酯（EP）已被报道在几种I/R模型中抑制HMGB 1的释放。本研究旨在探讨HMGB 1在大鼠心肌I/R模型中的潜在作用以及EP的影响。雄性Sprague道利大鼠进行30 min心肌缺血和48 h再灌注。在方案1中，将大鼠分配到四个组之一（n=16/组）：磷酸盐缓冲盐水（PBS）或三种不同剂量（1、10或100 μg/kg）的重组人HMGB 1（rhHMGB 1）。在方案2中，大鼠也被分配到四个组之一（每组n=16）：假手术组、对照组、EP组和EP + rhHMGB 1组。再灌注前静脉注射EP（40 mg/kg）或rhHMGB 1（100 μg/kg）。进行血流动力学测量，并计算心肌梗死面积（IS）。Western blotting检测HMGB 1、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的表达水平。在方案1中，rhHMGB 1（100 μg/kg）组的IS较PBS组显著增加，且伴随TNF-α和IL-6水平的升高。在方案2大鼠中，与假手术组相比，I/R导致HMGB 1表达增加4.8倍，IS增加，心功能受损。EP可明显抑制HMGB 1的升高，抑制TNF-α和IL-6的活化，减轻心功能不全。这种心肌保护作用被rhHMGB 1所消除。总之，心肌I/R后HMGB 1的蓄积对心脏有害。EP可对心肌I/R损伤发挥强有力的保护作用，这些益处与HMGB 1的减少有关。
High-mobility group box-1 (HMGB1) acts as a proinflammatory cytokine that triggers and amplifies the inflammation cascade following ischemia/reperfusion (I/R). Ethyl pyruvate (EP) has been reported to inhibit HMGB1 release in several I/R models. This study was designed to investigate the potential role of HMGB1 in a rat myocardial I/R model and to determine the effect of EP. Male Sprague Dawley rats were subjected to 30 min myocardial ischemia and 48 h reperfusion. In protocol 1, the rats were assigned to one of four groups (n=16 per group): Phosphate-buffered saline (PBS) or recombinant human HMGB1 (rhHMGB1) at three different doses (1, 10 or 100 μg/kg). In protocol 2, the rats were also assigned to one of four groups (n=16 per group): Sham, control, EP and EP + rhHMGB1. EP (40 mg/kg) or rhHMGB1 (100 μg/kg) was injected intravenously prior to reperfusion. Hemodynamic measurements were performed, and myocardial infarct size (IS) was calculated. Western blotting was conducted to evaluate HMGB1, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression levels. In the protocol 1 rats, the IS was markedly increased in the rhHMGB1 (100 μg/kg) group compared with that in the PBS group, and this increase was accompanied by elevated levels of TNF-α and IL-6. In the protocol 2 rats, I/R resulted a 4.8-fold increase in HMGB1 expression with an increased IS and impaired cardiac function compared with the sham group. EP significantly inhibited the elevated HMGB1 level, suppressed the activated TNF-α and IL-6 and reduced cardiac dysfunction. This cardioprotection was abolished by rhHMGB1. In conclusion, accumulation of HMGB1 is deleterious to the heart following myocardial I/R. EP can exert a strong protective effect against myocardial I/R injury, and these benefits are associated with a reduction in HMGB1.
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影响因子：
4.6
作者：
Shen M;Lu J;Dai W;Wang F;Xu L;Chen K;He L;Cheng P;Zhang Y;Wang C;Wu D;Yang J;Zhu R;Zhang H;Zhou Y;Guo C
通讯作者：
Guo C
HMGB1：内源性危险信号。
影响因子：
5.7
作者：
Klune, John R.;Dhupar, Rajeev;Cardinal, Jon;Billiar, Timothy R.;Tsung, Allan
通讯作者：
Tsung, Allan
影响因子：
64.8
作者：
Scaffidi, P;Misteli, T;Bianchi, ME
通讯作者：
Bianchi, ME
影响因子：
8.3
作者：
Yu, YM;Kim, JB;Lee, JK
通讯作者：
Lee, JK
影响因子：
37.8
作者：
Andrassy, Martin;Volz, Hans C.;Bierhaus, Angelika
通讯作者：
Bierhaus, Angelika