Inhibiting Cardiac Mitochondrial Fatty Acid Oxidation Attenuates Myocardial Injury in a Rat Model of Cardiac Arrest.
Inhibiting Cardiac Mitochondrial Fatty Acid Oxidation Attenuates Myocardial Injury in a Rat Model of Cardiac Arrest.
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抑制心脏线粒体脂肪酸氧化减轻心脏骤停大鼠模型的心肌损伤。
DOI：
10.1155/2021/6622232
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发表时间：
2021
影响因子：
--
通讯作者：
Yao L
中科院分区：
文献类型：
--
作者：
Wang P;Zhang F;Pan L;Tan Y;Song F;Ge Q;Huang Z;Yao L
线粒体脂肪酸氧化（FAO）参与心肺复苏（CPR）后的心肌损伤。本研究旨在探讨抑制线粒体FAO对心肌损伤的影响以及复苏后心肌功能障碍的潜在机制。诱导大鼠，进行 8 分钟的心室颤动，并进行 6 分钟的心肺复苏。将恢复自主循环（ROSC）的大鼠随机分为Sham组、CPR组和CPR + 曲美他嗪（TMZ）组。 CPR++TMZ组大鼠在ROSC开始时通过右颈外静脉注射TMZ（10mg/kg），而CPR组大鼠注射等体积的载体。假手术大鼠仅施用等体积的媒介物。我们发现ROSC后与心脏线粒体FAO相关的酶活性得到部分改善。 TMZ 作为 3-酮脂酰 CoA 硫解酶的可逆抑制剂，在 ROSC 后抑制心肌线粒体FAO。在 CPR + TMZ 组中，ROSC 后心肌损伤和氧化应激减弱，心脏组织中线粒体损伤水平得到缓解。此外，心脏线粒体代谢紊乱得到改善，具体而言，ROSC后施用TMZ抑制心肌线粒体FAO，从而减少与线粒体活性氧（ROS）生成相关的多余琥珀酸。总之，在ROSC后的早期，抑制心脏线粒体FAO可以减轻心脏ROS的过度生成并保留心肌功能，这可能是通过减轻心脏骤停大鼠模型中心脏线粒体代谢功能障碍来实现的。
Mitochondrial fatty acid oxidation (FAO) is involved in myocardial damage after cardiopulmonary resuscitation (CPR). This study is aimed at investigating the effect of inhibiting mitochondrial FAO on myocardial injury and the underlying mechanisms of postresuscitation myocardial dysfunction. Rats were induced, subjected to 8 min of ventricular fibrillation, and underwent 6 min of CPR. Rats with return of spontaneous circulation (ROSC) were randomly divided into the Sham group, CPR group, and CPR + Trimetazidine (TMZ) group. Rats in the CPR + TMZ group were administered TMZ (10 mg/kg) at the onset of ROSC via the right external jugular vein, while rats in the CPR group were injected with equivalent volumes of vehicle. The sham rats were only administered equivalent volumes of vehicle. We found that the activities of enzymes related to cardiac mitochondrial FAO were partly improved after ROSC. TMZ, as a reversible inhibitor of 3-ketoacyl CoA thiolase, inhibited myocardial mitochondrial FAO after ROSC. In the CPR + TMZ group, the levels of mitochondrial injury in cardiac tissue were alleviated following attenuated myocardial damage and oxidative stress after ROSC. In addition, the disorder of cardiac mitochondrial metabolism was ameliorated, and specifically, the superfluous succinate related to mitochondrial reactive oxygen species (ROS) generation was decreased by inhibiting myocardial mitochondrial FAO with TMZ administration after ROSC. In conclusion, in the early period after ROSC, inhibiting cardiac mitochondrial FAO attenuated excessive cardiac ROS generation and preserved myocardial function, probably by alleviating the dysfunction of cardiac mitochondrial metabolism in a rat model of cardiac arrest.
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DOI：
10.3390/antiox7010013
发表时间：
2018-01-16
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
--
作者：
Ježek J;Cooper KF;Strich R
通讯作者：
Strich R
影响因子：
--
作者：
Jentzer JC;Chonde MD;Dezfulian C
通讯作者：
Dezfulian C
影响因子：
3.7
作者：
Goguadze, Nino;Zhuravliova, Elene;Maurice, Tangui
通讯作者：
Maurice, Tangui
影响因子：
5.4
作者：
Moreno-Sanchez, Rafael;Hernandez-Esquivel, Luz;Rodriguez-Enriquez, Sara
通讯作者：
Rodriguez-Enriquez, Sara
影响因子：
5
作者：
Andrienko TN;Pasdois P;Pereira GC;Ovens MJ;Halestrap AP
通讯作者：
Halestrap AP