Hypercholesterolemic myocardium is vulnerable to ischemia-reperfusion injury and refractory to sevoflurane-induced protection.
Hypercholesterolemic myocardium is vulnerable to ischemia-reperfusion injury and refractory to sevoflurane-induced protection.
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高胆固醇血症心肌易受缺血再灌注损伤且难以抵抗七氟烷诱导的保护
DOI：
10.1371/journal.pone.0076652
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wang JA
中科院分区：
文献类型：
--
作者：
Xu Y;Ma LL;Zhou C;Zhang FJ;Kong FJ;Wang WN;Qian LB;Wang CC;Liu XB;Yan M;Wang JA
最近的研究表明，挥发性麻醉剂后处理通过激活再灌注损伤挽救激酶(Risk)通路，对缺血再灌注(IR)损伤具有心肌保护作用。因为已证明高胆固醇血症会降低风险。因此，我们调查麻醉剂诱导的心脏保护在高胆固醇血症大鼠中是否保持。在本研究中，正常胆脂血症和高胆固醇血症大鼠心脏分别进行30min和2 h的缺血再灌流。动物给予2.4%七氟醚5min或3个周期的10-S缺血/10-S再灌流。连续监测左心室发展压、左心室舒张末压和心率等血流动力学参数。测定心肌梗死面积、细胞凋亡率、p-Akt、p-ERK1/2、p-GSK3β。我们发现，七氟醚和缺血后处理均能显著改善健康大鼠的心泵功能，缩小心肌梗死面积，增加Akt、ERK1/2及其下游靶Gsk3β的磷酸化。在高胆固醇血症大鼠，七氟醚和缺血后处理都不能改善左室血流动力学，缩小梗塞面积，增加磷酸化的Akt、ERK1/2和Gsk3β。相比之下，GSK抑制剂SB216763对健康和高胆固醇血症心脏的IR损伤具有心脏保护作用。结论：高胆固醇血症通过改变GSK_3β上游信号转导通路和急性抑制GSK可能为高胆固醇血症心脏抗IR损伤提供了新的治疗策略。
Recent studies have demonstrated that volatile anesthetic postconditioning confers myocardial protection against ischemia-reperfusion (IR) injury through activation of the reperfusion injury salvage kinase (RISK) pathway. As RISK has been shown to be impaired in hypercholesterolemia. Therefore, we investigate whether anesthetic-induced cardiac protection was maintained in hypercholesterolemic rats. In the present study, normocholesteolemic or hypercholesterolemic rat hearts were subjected to 30 min of ischemia and 2 h of reperfusion. Animals received 2.4% sevoflurane for 5 min or 3 cycles of 10-s ischemia/10-s reperfusion. The hemodynamic parameters, including left ventricular developed pressure, left ventricular end-diastolic pressure and heart rate, were continuously monitored. The infarct size, apoptosis, p-Akt, p-ERK1/2, p-GSK3β were determined. We found that both sevoflurane and ischemic postconditioning significantly improved heart pump function, reduced infarct size and increased the phosphorylation of Akt, ERK1/2 and their downstream target of GSK3β in the healthy rats. In the hypercholesterolemic rats, neither sevoflurane nor ischemic postconditioning improved left ventricular hemodynamics, reduced infarct size and increased the phosphorylated Akt, ERK1/2 and GSK3β. In contrast, GSK inhibitor SB216763 conferred cardioprotection against IR injury in healthy and hypercholesterolemic hearts. In conclusions, hyperchoesterolemia abrogated sevoflurane-induced cardioprotection against IR injury by alteration of upstream signaling of GSK3β and acute GSK inhibition may provide a novel therapeutic strategy to protect hypercholesterolemic hearts against IR injury.
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影响因子：
9.5
作者：
Mykytenko, James;Kerendi, Faraz;Zhao, Zhi-Qing
通讯作者：
Zhao, Zhi-Qing
影响因子：
4.8
作者：
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SPADY, DK
DOI：
10.1152/ajpheart.00484.2009
发表时间：
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37.8
作者：
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影响因子：
37.8
作者：
Cao, Chun-Mei;Zhang, Yan;Xiao, Rui-Ping
通讯作者：
Xiao, Rui-Ping