Li Jiu-Kang, Song Zhi-Ping, Hou Xing-Zhi
Department of Infectious Diseases, The People's Hospital of Yue Chi County, Guang'an, Sichuan 638300, P.R. China.
Department of Cardiovascular Medicine, The People's Hospital of Yue Chi County, Guang'an, Sichuan 638300, P.R. China.
Exp Ther Med. 2023 Feb 17;25(4):155. doi: 10.3892/etm.2023.11854. eCollection 2023 Apr.
Ischemic heart disease is a common cardiovascular disease. Scutellarin (SCU) exhibits protective effects in ischemic cardiomyocytes; however, to the best of our knowledge, the protective mechanism of SCU remains unclear. The present study was performed to investigate the protective effect of SCU on cardiomyocytes after ischemia/reperfusion (I/R) injury and the underlying mechanism. Mice were intraperitoneally injected with SCU (20 mg/kg) for 7 days before establishing the heart I/R injury model. Cardiac function was detected using small animal echocardiography, apoptotic cells were visualized using TUNEL staining, the myocardial infarct area was assessed by 2,3,5-triphenyltetrazolium chloride staining, and the protein levels of cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), Bcl-2, Bax and cleaved Caspase-3 were detected by western blotting. In experiments, H9c2 cells were pretreated with SCU, RU.521 (cGAS inhibitor) and H-151 (STING inhibitor), before cell hypoxia/reoxygenation (H/R) injury. The viability of H9c2 cells was detected using a Cell Counting Kit-8 assay, the rate of apoptosis was determined by flow cytometry, and the protein expression levels of cGAS, STING, Bcl-2, Bax and cleaved Caspase-3 were detected by western blotting. It was revealed that SCU ameliorated cardiac dysfunction and apoptosis, and inhibited the activation of the cGAS-STING and Bcl-2/Bax/Caspase-3 signaling pathways in I/R-injured mice. It was also observed that SCU significantly increased cell viability and decreased apoptosis in H/R-induced H9c2 cells. Furthermore, H/R increased the expression levels of cGAS, STING and cleaved Caspase-3, and decreased the ratio of Bcl-2/Bax, which could be reversed by treatment with SCU, RU.521 and H-151. The present study demonstrated that the cGAS-STING signaling pathway may be involved in the regulation of the activation of the Bcl-2/Bax/Caspase-3 signaling pathway to mediate I/R-induced cardiomyocyte apoptosis and cardiac dysfunction, which could be ameliorated by SCU treatment.
缺血性心脏病是一种常见的心血管疾病。灯盏花素（SCU）对缺血性心肌细胞具有保护作用；然而，据我们所知，SCU的保护机制仍不清楚。本研究旨在探讨SCU对心肌缺血/再灌注（I/R）损伤后心肌细胞的保护作用及其潜在机制。在建立心脏I/R损伤模型前7天，给小鼠腹腔注射SCU（20mg/kg）。使用小动物超声心动图检测心脏功能，用TUNEL染色观察凋亡细胞，用氯化三苯基四氮唑染色评估心肌梗死面积，并用蛋白质印迹法检测环磷酸鸟苷-腺苷酸合成酶（cGAS）、干扰素基因刺激因子（STING）、Bcl-2、Bax和裂解型半胱天冬酶-3的蛋白水平。在实验中，在细胞缺氧/复氧（H/R）损伤前，用SCU、RU.521（cGAS抑制剂）和H-151（STING抑制剂）预处理H9c2细胞。使用细胞计数试剂盒-8检测H9c2细胞的活力，通过流式细胞术测定凋亡率，并用蛋白质印迹法检测cGAS、STING、Bcl-2、Bax和裂解型半胱天冬酶-3的蛋白表达水平。结果显示，SCU改善了I/R损伤小鼠的心脏功能障碍和细胞凋亡，并抑制了cGAS-STING和Bcl-2/Bax/Caspase-3信号通路的激活。还观察到，SCU显著提高了H/R诱导的H9c2细胞的活力并降低了细胞凋亡。此外，H/R增加了cGAS、STING和裂解型半胱天冬酶-3的表达水平，并降低了Bcl-2/Bax的比值，而SCU、RU.521和H-151处理可使其逆转。本研究表明，cGAS-STING信号通路可能参与调节Bcl-2/Bax/Caspase-3信号通路的激活，以介导I/R诱导的心肌细胞凋亡和心脏功能障碍，而SCU治疗可改善这种情况。
