Department of Cardiothoracic, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei 434023, P.R. China.
Department of Oncology, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei 434023, P.R. China.
Mol Med Rep. 2020 Oct;22(4):3151-3160. doi: 10.3892/mmr.2020.11396. Epub 2020 Jul 31.
Icariside II (ICAII) is a bioflavonoid compound which has demonstrated anti‑oxidative, anti‑inflammatory and anti‑apoptotic biological activities. However, to the best of our knowledge, whether ICAII can alleviate myocardial ischemia and reperfusion injury (MIRI) remains unknown. The aim of the present study was to determine whether ICAII exerted a protective effect on MIRI and to investigate the potential underlying mechanism of action. A rat MIRI model was established by ligation of the left anterior descending coronary artery for 30 min, followed by a 24 h reperfusion. Pretreatment with ICAII with or without a PI3K/AKT inhibitor was administered at the beginning of reperfusion. Morphological and histological analyses were detected using hematoxylin and eosin staining; the infarct size was measured using Evans blue and 2,3,5‑triphenyltetrazolium chloride staining; and plasma levels of lactate dehydrogenase (LDH) and creatine kinase‑myocardial band (CK‑MB) were analyzed using commercialized assay kits. In addition, the cardiac function was evaluated by echocardiography and the levels of cardiomyocyte apoptosis were determined using a TUNEL staining. The protein expression levels of Bax, Bcl‑2, cleaved caspase‑3, interleukin‑6, tumor necrosis factor‑α, PI3K, phosphorylated (p)‑PI3K, AKT and p‑AKT were analyzed using western blotting analysis. ICAII significantly reduced the infarct size, decreased the release of LDH and CK‑MB and improved the cardiac function induced by IR injury. Moreover, ICAII pretreatment significantly inhibited myocardial apoptosis and the inflammatory response. ICAII also upregulated the expression levels of p‑PI3K and p‑AKT. However, the protective effects of ICAII were abolished by an inhibitor (LY294002) of the PI3K/AKT signaling pathway. In conclusion, the findings of the present study suggested that ICAII may mitigate MIRI by activating the PI3K/AKT signaling pathway.
二氢杨梅素（ICAII）是一种生物类黄酮化合物，具有抗氧化、抗炎和抗细胞凋亡的生物学活性。然而，据我们所知，ICAII 是否能减轻心肌缺血再灌注损伤（MIRI）尚不清楚。本研究旨在确定 ICAII 是否对 MIRI 具有保护作用，并探讨其潜在的作用机制。通过结扎左前降支冠状动脉 30min 后再灌注 24h 建立大鼠 MIRI 模型。在再灌注开始时用 ICAII 预处理，或用 PI3K/AKT 抑制剂预处理。通过苏木精和伊红染色进行形态和组织学分析；通过 Evans 蓝和 2,3,5-三苯基氯化四唑染色测量梗死面积；通过商业化试剂盒分析血浆乳酸脱氢酶（LDH）和肌酸激酶同工酶-MB（CK-MB）水平。此外，通过超声心动图评估心功能，通过 TUNEL 染色测定心肌细胞凋亡水平。通过 Western blot 分析检测 Bax、Bcl-2、cleaved caspase-3、白细胞介素-6、肿瘤坏死因子-α、PI3K、磷酸化（p）-PI3K、AKT 和 p-AKT 的蛋白表达水平。ICAII 显著减少梗死面积，降低 LDH 和 CK-MB 的释放，改善 IR 损伤引起的心脏功能。此外，ICAII 预处理显著抑制心肌细胞凋亡和炎症反应。ICAII 还上调了 p-PI3K 和 p-AKT 的表达水平。然而，PI3K/AKT 信号通路抑制剂（LY294002）抑制了 ICAII 的保护作用。综上所述，本研究结果表明，ICAII 通过激活 PI3K/AKT 信号通路可能减轻 MIRI。
