Pan Rongrong, Zhuang Qin, Wang Jiangtin
Department of Cardiology, Cixi People's Hospital, Wenzhou Medical University, Cixi, Zhejiang 315300, P.R. China.
Department of Cardiology, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China.
Exp Ther Med. 2021 Nov;22(5):1307. doi: 10.3892/etm.2021.10742. Epub 2021 Sep 16.
Ononin (ON) is an isoflavone with numerous reported bioactivities, including anti-oxidative, anti-inflammatory and neuroprotective effects. Autophagy is a critical homeostatic process in the body that has been reported to closely associate with the apoptotic processes of cardiomyocytes. Using flow cytometry, western blotting, echocardiography and Masson's staining, the present study investigated the effects of ON on HO-induced cardiomyocyte apoptosis and myocardial infarction, in addition to any potential underlying molecular mechanisms. HO treatment reliably induced apoptosis in H9C2 cells. The anti-apoptotic effects of ON were revealed by flow cytometry results and by the downregulation of cleaved-caspase 3. Further investigations indicated that ON may alleviate apoptosis by enhancing autophagy, as evidenced by increased microtubule-associated proteins 1A/1B light chain 3B expression and p62 degradation. Activation of the 5' AMP-activated protein kinase (AMPK)/mTOR pathway was observed after ON administration following HO-induced cardiomyocyte injury. However, these anti-apoptotic effects mediated by ON were lost after autophagy inhibition by chloroquine or AMPK inhibition by Compound C. Finally, the protective effects of ON on cardiomyocytes could also be observed . A myocardial infarction model was established by ligating the left anterior descending branch of the rat heart. Using echocardiography and Masson's staining, ON was shown to increase the ejection fraction and decrease cardiac fibrosis in rats with myocardial infarction. These results suggest that ON exerts cardioprotective effects by improving autophagy via the AMPK/mTOR signaling pathway.
芒柄花素（ON）是一种异黄酮，有众多已报道的生物活性，包括抗氧化、抗炎和神经保护作用。自噬是体内一个关键的稳态过程，据报道与心肌细胞的凋亡过程密切相关。本研究使用流式细胞术、蛋白质印迹法、超声心动图和Masson染色，研究了芒柄花素对过氧化氢（HO）诱导的心肌细胞凋亡和心肌梗死的影响，以及任何潜在的分子机制。HO处理可可靠地诱导H9C2细胞凋亡。流式细胞术结果和裂解型半胱天冬酶-3的下调揭示了芒柄花素的抗凋亡作用。进一步研究表明，芒柄花素可能通过增强自噬来减轻凋亡，微管相关蛋白1A/1B轻链3B表达增加和p62降解证明了这一点。在HO诱导心肌细胞损伤后给予芒柄花素后，观察到5'单磷酸腺苷激活的蛋白激酶（AMPK）/雷帕霉素靶蛋白（mTOR）通路的激活。然而，在用氯喹抑制自噬或用化合物C抑制AMPK后，芒柄花素介导的这些抗凋亡作用消失。最后，也观察到了芒柄花素对心肌细胞的保护作用。通过结扎大鼠心脏左前降支建立心肌梗死模型。使用超声心动图和Masson染色，结果显示芒柄花素可增加心肌梗死大鼠的射血分数并减少心脏纤维化。这些结果表明，芒柄花素通过AMPK/mTOR信号通路改善自噬发挥心脏保护作用。
