Hongjingtian injection protects against myocardial ischemia reperfusion-induced apoptosis by blocking ROS induced autophagic- flux
Hongjingtian injection protects against myocardial ischemia reperfusion-induced apoptosis by blocking ROS induced autophagic- flux
复制标题
红景天注射液通过阻断ROS诱导的自噬流来防止心肌缺血再灌注诱导的细胞凋亡。
DOI：
10.1016/j.biopha.2020.111205
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发表时间：
2021-01-01
影响因子：
7.5
通讯作者：
Zhang, Ling
中科院分区：
文献类型：
--
作者：
Zhao, Jing;Zhang, Jiwei;Zhang, Ling
背景：红景天注射液在我国已广泛应用于临床治疗冠心病。然而，治疗的潜在机制仍然需要说明。本研究的目的是确定是否HJT保护心肌缺血再灌注损伤通过活性氧（ROS）诱导的自噬通量和凋亡，如果是的话，探讨潜在的mechanism.Methods：在体内心肌保护和自噬调节HJT在心肌缺血再灌注损伤C57 BL/6 J和CAG-RFP-EGFP-LC 3转基因C57 BL/6 J小鼠。在体外，观察HJT对H2 O2诱导的H9 c2细胞凋亡、自噬通量、氧化应激和线粒体功能的影响。结果：HJT能显著降低C57 BL/6 J小鼠心肌缺血再灌注损伤后的梗死面积，减少心肌细胞凋亡。HJT可降低CAG-RFP-EGFP-LC 3转基因C57 BL/6 J小鼠心肌缺血再灌注损伤后的自噬流量。HJT通过显著降低caspase-3的水平和增加Bcl-2/Bax比值来抑制H2 O2诱导的细胞凋亡。HJT通过显著降低LC 3-II和p-AMPK的表达和增加pmTOR来抑制H2 O2刺激后的自噬通量。结论：HJT治疗心肌缺血再灌注损伤的机制可能与其改善线粒体功能，通过AMPK/mTOR途径调节自噬抑制细胞凋亡有关。
Background: Hongjingtian injection (HJT) has been widely used in the clinic to treat coronary heart disease in China. However, the underlying mechanisms of therapies still need to be illustrated. The present study aims to determine whether HJT protects against myocardial ischemia reperfusion injury via Reactive Oxygen Species (ROS)-induced autophagic flux and apoptosis and, if so, to explore the underlying mechanisms.Methods: In vivo myocardial protection and autophagy regulation of HJT in myocardial ischemia reperfusion injury in C57BL/6 J and CAG-RFP-EGFP-LC3 transgenic C57BL/6 J mice were investigated. In vitro, the effects of HJT on apoptosis, autophagic flux, oxidative stress and mitochondrial function were observed in H2O2-induced H9c2 cells. In addition, apoptosis-related proteins and autophagy-related proteins were assessed to explore the underlying mechanisms.Results: HJT significantly decreased the infarct area and cell apoptosis after myocardial ischemia reperfusion injury in C57BL/6 J mice. Autophagic flux was reduced by HJT treatment after myocardial ischemia reperfusion injury in CAG-RFP-EGFP-LC3 transgenic C57BL/6 J mice. HJT inhibited H2O2 -induced cell apoptosis by significantly decreasing the levels of cleaved caspase 3 and increasing the Bcl-2/Bax ratio. HJT inhibited autophagic flux after H2O2 stimulation by significantly decreasing LC3-II and p-AMPK expression and increasing pmTOR. HJT inhibited ROS production and improved mitochondrial function in H2O2-induced cells by significantly increasing the mitochondrial membrane potential, intracellular ATP contents and oxygen consumption.Conclusion: The beneficial effects of HJT in treating myocardial ischemia reperfusion are partially due to improved mitochondrial function and regulated autophagy to inhibit cell apoptosis through the AMPK/mTOR pathway.