再灌注损伤
医学
线粒体
心肌保护
细胞凋亡
心肌梗塞
心功能曲线
缺血
p38丝裂原活化蛋白激酶
活性氧
蛋白激酶B
内科学
磷酸化
药理学
心脏病学
内分泌学
蛋白激酶A
化学
细胞生物学
生物
生物化学
心力衰竭
作者
Wen Jiang,Yuxiang Zhang,Wei Zhang,Xiaomei Pan,Jieyu Liu,Qiang Chen,Junhui Chen
标识
DOI:10.1080/10641963.2023.2192444
摘要
Acute myocardial infarction (AMI) is the leading cause of death worldwide. Ischemia-reperfusion (I/R) injury is considered the most common contributor to AMI. Hirsutine has been shown to protect cardiomyocytes against hypoxic injury. The present study investigated whether hirsutine improved AMI induced by I/R injury and the underlying mechanisms. In our study, we used a rat model of myocardial I/R injury. The rats were given hirsutine daily (5, 10, 20 mg/kg) by gavage for 15 days before the myocardial I/R injury. Detectable changes were observed in myocardial infarct size, mitochondrial function, histological damage, and cardiac cell apoptosis. According to our findings, hirsutine pre-treatment reduced the myocardial infarct size, enhanced cardiac function, inhibited cell apoptosis, reduced the tissue lactate dehydrogenase (LDH) and reactive oxygen species (ROS) content, as well as enhanced myocardial ATP content and mitochondrial complex activity. In addition, hirsutine balanced mitochondrial dynamics by increasing Mitofusin2 (Mfn2) expression while decreasing dynamin-related protein 1 phosphorylation (p-Drp1), which was partially regulated by ROS and calmodulin-dependent protein kinase II phosphorylation (p-CaMKII). Mechanistically, hirsutine inhibited mitochondrial-mediated apoptosis during I/R injury by blocking the AKT/ASK-1/p38 MAPK pathway. This present study provides a promising therapeutic intervention for myocardial I/R injury.
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