乌头碱通过促进活性氧激活的P38/丝裂原活化蛋白激酶/核因子E2相关因子2信号通路抑制自噬并加重心肌损伤。
Aconitine promotes ROS-activated P38/MAPK/Nrf2 pathway to inhibit autophagy and promote myocardial injury.
作者信息
Yang Chunai, Fu Jinxiao, Zheng Fenshuang, Fu Yangshan, Duan Xueqiong, Zuo Ruiling, Zhu Junbo
机构信息
Department of Emergency, The Affiliated Hospital of Yunnan University, Kunming, 650021, China.
Department of Geriatric Medicine, The Affiliated Hospital of Yunnan University, 176 Qingnian Road, Wuhua District, Kunming, 650021, Yunnan, China.
出版信息
J Cardiothorac Surg. 2024 Dec 20;19(1):665. doi: 10.1186/s13019-024-03149-0.
BACKGROUND
Aconitine has cardiotoxicity, but the mechanism of cardiotoxicity induced by aconitine is limited. The aim of this study was to investigate the mechanism of myocardial injury induced by aconitine.
METHODS
Using aconitine, ROS inhibitor N-acetylcysteine(NAC), the autophagy activitor Rapamycin (Rap) or the P38/MAPK pathway activitor Dehydrocorydaline treats H9C2 cells. CCK-8 assay was used to assay cell proliferation activity. Flow Cytometry was used to detect cell apoptosis. Dichloro-dihydrofluorescein diacetate was used to detect ROS levels. The expression of LC3 was detected by Immunofluorescence Staining. Western blotting detected the expression of related proteins. The mRNA levels of inflammatory factors were detected by RT-qPCR.
RESULTS
Aconitine inhibits cardiomyocyte proliferation, induces apoptosis and secretion of inflammatory factors. Aconitine activates the P38/MAPK/Nrf2 pathway, induces ROS increase, and promotes autophagy. NAC can inhibit proliferation inhibition, apoptosis, inflammation and P38/MAPK/Nrf2 pathway activation induced by aconitine. Rap and P38 activators can partially recover the effects of NAC on proliferation, apoptosis, inflammation and autophagy of cardiomyocytes.
CONCLUSION
Aconitine promotes ROS-activated P38/MAPK/Nrf2 pathway to inhibit autophagy and promote myocardial injury.
背景
乌头碱具有心脏毒性，但乌头碱诱导心脏毒性的机制尚不清楚。本研究旨在探讨乌头碱诱导心肌损伤的机制。
方法
用乌头碱、活性氧抑制剂N-乙酰半胱氨酸（NAC）、自噬激活剂雷帕霉素（Rap）或P38/丝裂原活化蛋白激酶（MAPK）途径激活剂脱氢紫堇碱处理H9C2细胞。采用CCK-8法检测细胞增殖活性。采用流式细胞术检测细胞凋亡。用二氯二氢荧光素二乙酸酯检测活性氧水平。通过免疫荧光染色检测微管相关蛋白1轻链3（LC3）的表达。蛋白质免疫印迹法检测相关蛋白的表达。通过逆转录-定量聚合酶链反应（RT-qPCR）检测炎症因子的mRNA水平。
结果
乌头碱抑制心肌细胞增殖，诱导细胞凋亡和炎症因子分泌。乌头碱激活P38/MAPK/核因子E2相关因子2（Nrf2）途径，诱导活性氧增加，并促进自噬。NAC可抑制乌头碱诱导的增殖抑制、细胞凋亡、炎症和P38/MAPK/Nrf2途径激活。Rap和P38激活剂可部分恢复NAC对心肌细胞增殖、凋亡、炎症和自噬的影响。
结论
乌头碱通过促进活性氧激活的P38/MAPK/Nrf2途径抑制自噬并促进心肌损伤。
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