Melatonin improves neurological outcomes and preserves hippocampal mitochondrial function in a rat model of cardiac arrest.
Melatonin improves neurological outcomes and preserves hippocampal mitochondrial function in a rat model of cardiac arrest.
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褪黑素可改善心脏骤停大鼠模型的神经系统结果并保留海马线粒体功能
DOI：
10.1371/journal.pone.0207098
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Li T
中科院分区：
文献类型：
--
作者：
Yang L;Wang J;Deng Y;Gong C;Li Q;Chen Q;Li H;Jiang C;Zhou R;Hai K;Wu W;Li T
心脏骤停（CA）/心肺复苏（CPR）后的脑损伤与CA幸存者的预后不良有关。本研究旨在评估褪黑激素对复苏后神经功能结局的影响并探讨其潜在机制。将SD大鼠随机分为假手术组、心肺复苏组、褪黑素预处理组（Pre-M）和褪黑素后处理组（Post-M）。对于最后2组，在大鼠从CA/CPR存活之前或之后24小时，每天进行褪黑激素管饲，连续12天。基线和自主循环恢复（ROSC）后，各组的心率（HR）、平均动脉压（MAP）和呼气末二氧化碳（ETCO 2）无统计学差异。然而，褪黑激素预处理或后处理显着改善神经功能缺损评分和记忆和空间学习能力后CA/CPR。进一步的研究表明，在褪黑激素处理下，复合物I和复合物II支持的线粒体呼吸大大增加。此外，褪黑激素治疗保留了海马结合己糖激酶II（HKII）和ATP水平，并抑制CA/CPR后海马中上调的蛋白质赖氨酸乙酰化。总之，使用大鼠窒息CA模型，我们已经证明，在CA/CPR之前或之后用褪黑激素治疗提供了有希望的神经保护作用，并且这种保护是通过增加线粒体HKII表达、抑制蛋白乙酰化和改善海马线粒体功能来介导的。
Cerebral injury after cardiac arrest (CA)/cardiopulmonary resuscitation (CPR) has been implicated in the poor prognosis of CA survivors. This study was designed to evaluate the impact of melatonin on postresuscitation neurological outcomes and to explore the underlying mechanism. Sprague-Dawley rats were randomly assigned to four groups: sham group, CPR group, melatonin pretreatment group (Pre-M) and posttreatment group (Post-M). For the last 2 groups, daily melatonin gavage was performed for 12 consecutive days before or 24 hours after rat survival from CA/CPR. No statistical differences were observed in heart rate (HR), mean arterial blood pressure (MAP), and end-tidal carbon dioxide (ETCO2) at baseline and after restoration of spontaneous circulation (ROSC) among groups. However, melatonin pretreatment or posttreatment significantly improved neurological deficit score and memory and spatial learning ability after CA/CPR. Further studies demonstrated that the complex I- and complex-II supported mitochondrial respiration were greatly increased under melatonin treatment. In addition, melatonin treatment preserved the mitochondrial-binding hexokinase II (HKII) and ATP levels and suppressed the upregulated protein lysine acetylation in hippocampus after CA/CPR. In conclusion, using a rat asphyxial CA model we have demonstrated that treatment with melatonin either before or after CA/CPR provides a promising neuroprotective effect, and this protection was mediated by increasing mitochondrial HKII expression, suppressing protein acetylation and improving mitochondrial function in hippocampus.
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影响因子：
5.4
作者：
Kilbaugh TJ;Sutton RM;Karlsson M;Hansson MJ;Naim MY;Morgan RW;Bratinov G;Lampe JW;Nadkarni VM;Becker LB;Margulies SS;Berg RA
通讯作者：
Berg RA
影响因子：
10.3
作者：
Schaefer, Meike;Hardeland, Rudiger
通讯作者：
Hardeland, Rudiger
影响因子：
29
作者：
Qiu, Xiaolei;Brown, Katharine;Chen, Danica
通讯作者：
Chen, Danica
DOI：
10.1073/pnas.1705768114
发表时间：
2017-09-19
影响因子：
11.1
作者：
Suofu, Yalikun;Li, Wei;Friedlander, Robert M.
通讯作者：
Friedlander, Robert M.
影响因子：
29
作者：
Mitchell SJ;Madrigal-Matute J;Scheibye-Knudsen M;Fang E;Aon M;González-Reyes JA;Cortassa S;Kaushik S;Gonzalez-Freire M;Patel B;Wahl D;Ali A;Calvo-Rubio M;Burón MI;Guiterrez V;Ward TM;Palacios HH;Cai H;Frederick DW;Hine C;Broeskamp F;Habering L;Dawson J;Beasley TM;Wan J;Ikeno Y;Hubbard G;Becker KG;Zhang Y;Bohr VA;Longo DL;Navas P;Ferrucci L;Sinclair DA;Cohen P;Egan JM;Mitchell JR;Baur JA;Allison DB;Anson RM;Villalba JM;Madeo F;Cuervo AM;Pearson KJ;Ingram DK;Bernier M;de Cabo R
通讯作者：
de Cabo R