Therapeutic potentials of cell death inhibitors in rats with cardiac ischaemia/reperfusion injury

被引：28

作者：

Luo, Ying ^{[1
,2
,3
]}

Apaijai, Nattayaporn ^{[1
,2
,3
]}

Liao, Suchan ^{[1
,2
,3
]}

Maneechote, Chayodom ^{[1
,2
]}

Chunchai, Titikorn ^{[1
,2
]}

Arunsak, Busarin ^{[1
,2
]}

Benjanuwattra, Juthipong ^{[1
,2
]}

Yanpiset, Panat ^{[1
,2
,3
]}

Chattipakorn, Siriporn C. ^{[1
,2
,4
]}

Chattipakorn, Nipon ^{[1
,2
,3
]}

机构：

[1] Chiang Mai Univ, Fac Med, Cardiac Electrophysiol Res & Training Ctr, Chiang Mai 50200, Thailand

[2] Chiang Mai Univ, Ctr Excellence Cardiac Electrophysiol Res, Chiang Mai, Thailand

[3] Chiang Mai Univ, Fac Med, Dept Physiol, Cardiac Electrophysiol Unit, Chiang Mai, Thailand

[4] Chiang Mai Univ, Fac Dent, Dept Oral Biol & Diagnost Sci, Chiang Mai, Thailand

来源：

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE | 2022年 / 26卷 / 08期

关键词：

apoptosis; cardiac ischaemia; reperfusion injury; ferroptosis; mitochondria; necroptosis; ISCHEMIA-REPERFUSION INJURY; ACUTE MYOCARDIAL-INFARCTION; CASPASE INHIBITION; APOPTOSIS; SIZE; MITOCHONDRIA; FERROPTOSIS; ROLES;

D O I：

10.1111/jcmm.17275

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Growing evidence demonstrated that cell death pathways including ferroptosis, apoptosis and necroptosis contribute to cardiac ischaemia/reperfusion (I/R) injury. We hypothesized that ferroptosis, apoptosis and necroptosis contribute differently to myocardial damage during acute cardiac I/R injury. Rats underwent cardiac I/R or sham operation. I/R-operated rats were divided into 4 groups: vehicle, apoptosis (Z-vad), ferroptosis (Fer-1) and necroptosis (Nec-1) inhibition. Rats in each cell death inhibitor group were subdivided into 3 different dose regimens: low, medium and high. Infarct size, left ventricular (LV) function, arrhythmias and molecular mechanism were investigated. Cardiac I/R caused myocardial infarction, LV dysfunction, arrhythmias, mitochondrial dysfunction, mitochondrial dynamic imbalance, inflammation, apoptosis and ferroptosis. Infarct size, LV dysfunction, mitochondrial dysfunction, apoptosis and ferroptosis were all reduced to a similar extent in rats treated with Z-vad (low and medium doses) or Fer-1 (medium and high doses). Fer-1 treatment also reduced mitochondrial dynamic imbalance and inflammation. No evidence of necroptosis was found in association with acute I/R injury, therefore Nec-1 treatment could not be assessed. Apoptosis and ferroptosis, not necroptosis, contributed to myocardial damage in acute I/R injury. Inhibitors of these 2 pathways provided effective cardioprotection in rats with I/R injury though modulation of mitochondrial function and attenuated apoptosis and ferroptosis.

引用

页码：2462 / 2476

页数：15