Sarcoplasmic phospholamban protein is involved in the mechanisms of postresuscitation myocardial dysfunction and the cardioprotective effect of nitrite during resuscitation.

Sarcoplasmic phospholamban protein is involved in the mechanisms of postresuscitation myocardial dysfunction and the cardioprotective effect of nitrite during resuscitation.
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肌浆磷脂班蛋白参与复苏后心肌功能障碍的机制以及复苏过程中亚硝酸盐的心脏保护作用。

DOI:
10.1371/journal.pone.0082552
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Yang M
Yang M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Huang Y;He Q;Zhan L;Yang M

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肌浆网钙调控蛋白在急性缺血再灌注损伤后心肌功能障碍中起重要作用。我们推测,亚硝酸盐将改善复苏后心肌功能障碍,通过增加一氧化氮(NO)的产生,这种保护的机制是有关的SR钙处理蛋白的调制。我们使用雄性Sprague-Dawley大鼠进行了一项随机前瞻性动物研究。通过静脉推注氯化钾(40 µg/g)诱导心脏骤停。开始胸外按压时给予亚硝酸盐(1.2 nmol/g)或安慰剂。假手术组无心脏骤停。自主循环恢复(ROSC)后90分钟有创监测血流动力学参数。超声心动图检查评价心功能。在ROSC后5分钟和1小时收获心肌样品。复苏后,亚硝酸盐组和安慰剂组的心肌功能显著受损,而心脏功能(即,射血分数和缩短分数)在亚硝酸盐组中显著大于安慰剂组。与其他两组相比,亚硝酸盐给药增加了复苏后5分钟心肌中一氧化氮的水平。复苏后磷酸化受磷蛋白(PLB)水平降低,与安慰剂相比,亚硝酸盐增加了受磷蛋白的磷酸化。肌浆网Ca ~(2+)ATP酶(SERCA 2a)和兰尼碱受体(RyRs)的表达无明显差异。复苏后心肌功能障碍与PLB磷酸化受损有关。复苏期间给予亚硝酸盐通过在复苏期间保留磷酸化PLB蛋白来改善复苏后心肌功能障碍。
Sarcoplasmic reticulum (SR) Ca2+-handling proteins play an important role in myocardial dysfunction after acute ischemia/reperfusion injury. We hypothesized that nitrite would improve postresuscitation myocardial dysfunction by increasing nitric oxide (NO) generation and that the mechanism of this protection is related to the modulation of SR Ca2+-handling proteins. We conducted a randomized prospective animal study using male Sprague-Dawley rats. Cardiac arrest was induced by intravenous bolus of potassium chloride (40 µg/g). Nitrite (1.2 nmol/g) or placebo was administered when chest compression was started. No cardiac arrest was induced in the sham group. Hemodynamic parameters were monitored invasively for 90 minutes after the return of spontaneous circulation (ROSC). Echocardiogram was performed to evaluate cardiac function. Myocardial samples were harvested 5 minutes and 1 hour after ROSC. Myocardial function was significantly impaired in the nitrite and placebo groups after resuscitation, whereas cardiac function (i.e., ejection fraction and fractional shortening) was significantly greater in the nitrite group than in the placebo group. Nitrite administration increased the level of nitric oxide in the myocardium 5 min after resuscitation compared to the other two groups. The levels of phosphorylated phospholamban (PLB) were decreased after resuscitation, and nitrite increased the phosphorylation of phospholamban compared to the placebo. No significant differences were found in the expression of sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) and ryanodine receptors (RyRs). postresuscitation myocardial dysfunction is associated with the impairment of PLB phosphorylation. Nitrite administered during resuscitation improves postresuscitation myocardial dysfunction by preserving phosphorylated PLB protein during resuscitation.
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