Department of Pathology, College of Medicine, King Khalid University, Abha, Saudi Arabia.
Arch Physiol Biochem. 2024 Apr;130(2):215-229. doi: 10.1080/13813455.2021.2017463. Epub 2021 Dec 29.
This study investigated if acylated ghrelin (AG) could inhibit myocardial infarction (MI)-induced apoptosis in the left ventricles (LV) of male rats and tested if this protection involves modulating ARC anti-apoptotic protein. Rats ( = 12/group) were assigned as a sham-operated, a sham + AG (100 µg/kg, 2x/d, S.C.), MI, and MI + AG. With no antioxidant activity or expression of FAS, AG inhibited caspase-3, 8, and 9 and decreased cytosolic/mitochondrial levels of cytochrome-c, Bax, Bad, and Bad-BCL-2 complex in the LVs of the sham-operated and MI-treated rats. Concomitantly, AG preserved the mitochondria structure, decreased mtPTP, and enhanced state-3 respiration in the LVs of both treated groups. These effects were associated with increased mitochondrial levels of ARC and a reduction in the activity of calcineurin. Overall, AG suppresses MI-induced ventricular apoptosis by inhibition of calcineurin, activation of ARC, and preserving mitochondria integrity.
本研究旨在探讨酰化 ghrelin (AG) 是否可以抑制雄性大鼠左心室 (LV) 心肌梗死 (MI) 诱导的细胞凋亡，并检验这种保护作用是否涉及调节 ARC 抗凋亡蛋白。将大鼠（每组 n=12）分为假手术组、假手术+AG（100 µg/kg，2x/d，皮下注射）组、MI 组和 MI+AG 组。AG 无抗氧化活性，也不表达 FAS，可抑制 caspase-3、8 和 9 的活性，并降低 sham 操作和 MI 处理大鼠 LV 中的细胞质/线粒体细胞色素 c、Bax、Bad 和 Bad-BCL-2 复合物的水平。同时，AG 可维持线粒体结构，减少 mtPTP，并增强两种处理组的 LV 中的状态 3 呼吸。这些作用与线粒体 ARC 水平的增加以及钙调神经磷酸酶活性的降低有关。总的来说，AG 通过抑制钙调神经磷酸酶、激活 ARC 和维持线粒体完整性来抑制 MI 诱导的心室细胞凋亡。
