Sang Yiwei, Du Jiangnan, Zulikala Dilimulati, Sang Zhongqiang
Nature Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast, United Kingdom.
Dermatology Department, Shanghai Zhongye Hospital, Shanghai, China.
Front Pharmacol. 2024 Dec 24;15:1510380. doi: 10.3389/fphar.2024.1510380. eCollection 2024.
By far, one of the best treatments for myocardial ischemia is reperfusion therapy. The primary liposoluble component of Danshen, a traditional Chinese herbal remedy, Tanshinone ⅡA, has been shown to have cardiac healing properties. The purpose of this work is to investigate the processes by which Tanshinone ⅡA influences myocardial ischemia-reperfusion injury (MIRI) in the H9C2 cardiac myoblast cell line, as well as the association between Tanshinone ⅡA and MIRI.
The cardiac cells were divided into a normal group, a model group and Tanshinone ⅡA treatment groups. After 4 h of culture with the deprivation of oxygen and glucose, the cells were incubated normally for 2 h. The success of the model and the capacity of Tanshinone ⅡA to heal cardiac damage were validated by the outcomes of cell viability, morphology, and proliferation. The efficacy of Tanshinone ⅡA in treating MIRI was further confirmed by the scratch assay and biomarker measurement. The differentially expressed genes were examined using transcriptome sequencing. The Ataxia-Telangiectasia Mutated (ATM)/Growth Arrest and DNA Damage (GADD45)/Origin Recognition Complex (ORC) signaling pathway was identified as being crucial to this process by KEGG pathway analysis and GO enrichment. Molecular docking and RT-qPCR were used to confirm our results. The crucial function of the ATM/GADD45/ORC pathway was further confirmed by the addition of an ATM inhibitor, which inhibited the expression of ATM.
Tanshinone ⅡA can relieve the myocardial ischemia-reperfusion injury in cardiac cells by activating the ATM/GADD45/ORC pathway.
到目前为止，心肌缺血的最佳治疗方法之一是再灌注治疗。丹参是一种传统的中草药，其主要脂溶性成分丹参酮ⅡA已被证明具有心脏修复特性。这项工作的目的是研究丹参酮ⅡA影响H9C2心肌成肌细胞系中心肌缺血再灌注损伤（MIRI）的过程，以及丹参酮ⅡA与MIRI之间的关联。
将心肌细胞分为正常组、模型组和丹参酮ⅡA治疗组。在缺氧和无糖培养4小时后，将细胞正常培养2小时。通过细胞活力、形态和增殖结果验证模型的成功以及丹参酮ⅡA修复心脏损伤的能力。划痕试验和生物标志物测量进一步证实了丹参酮ⅡA治疗MIRI的疗效。使用转录组测序检查差异表达基因。通过KEGG通路分析和GO富集确定共济失调毛细血管扩张突变（ATM）/生长停滞和DNA损伤（GADD45）/起源识别复合物（ORC）信号通路对该过程至关重要。使用分子对接和RT-qPCR来证实我们的结果。通过添加ATM抑制剂抑制ATM的表达，进一步证实了ATM/GADD45/ORC通路的关键作用。
丹参酮ⅡA可通过激活ATM/GADD45/ORC通路减轻心肌细胞中的心肌缺血再灌注损伤。
