Mou Shan-Qi, Zhou Zi-Ying, Feng Hong, Zhang Nan, Lin Zheng, Aiyasiding Xiahenazi, Li Wen-Jing, Ding Wen, Liao Hai-Han, Bian Zhou-Yan, Tang Qi-Zhu
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
Cardiovascular Research Institute of Wuhan University, Wuhan, China.
Front Pharmacol. 2021 May 14;12:648688. doi: 10.3389/fphar.2021.648688. eCollection 2021.
Liquiritin (LIQ) is a traditional Chinese medicine that has been reported to regulate inflammation, oxidative stress and cell apoptosis. However, the beneficial effects of LIQ in lipopolysaccharides (LPS)-induced septic cardiomyopathy (SCM) has not been reported. The primary goal of this study was to investigate the effects of LIQ in LPS-induced SCM model. Mice were pre-treated with LIQ for 7 days before they were injected with LPS (10 mg/kg) for inducing SCM model. Echocardiographic analysis was used to evaluate cardiac function after 12 h of LPS injection. Thereafter, mice were sacrificed to collect hearts for molecular and histopathologic assays by RT-PCR, western-blots, immunohistochemical and terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) staining analysis respectively. AMPKα2 knockout (AMPKα2) mice were used to elucidate the mechanism of LIQ Neonatal rat cardiomyocytes (NRCMs) treated with or without LPS were used to further investigate the roles and mechanisms of LIQ experiments. LIQ administration attenuated LPS-induced mouse cardiac dysfunction and reduced mortality, based upon the restoration of EF, FS, LVEDs, heart rate, dp/dt max and dp/dt min deteriorated by LPS treatment. LIQ treatment also reduced mRNA expression of TNFα, IL-6 and IL-1β, inhibited inflammatory cell migration, suppressed cardiac oxidative stress and apoptosis, and improved metabolism. Mechanistically, LIQ enhanced the phosphorylation of AMP-activated protein kinase α2 (AMPKα2) and decreased the phosphorylation of mTORC1, IκBα and NFκB/p65. Importantly, the beneficial roles of LIQ were not observed in AMPKα2 knockout model, nor were they observed model after inhibiting AMPK activity with an AMPK inhibitor. We have demonstrated that LIQ exerts its protective effects in an SCM model induced by LPS administration. LIQ reduced inflammation, oxidative stress, apoptosis and metabolic alterations via regulating AMPKα2 dependent signaling pathway. Thus, LIQ might be a potential treatment or adjuvant for SCM treatment.
甘草苷（LIQ）是一种传统中药，据报道具有调节炎症、氧化应激和细胞凋亡的作用。然而，LIQ对脂多糖（LPS）诱导的脓毒症性心肌病（SCM）的有益作用尚未见报道。本研究的主要目的是探讨LIQ在LPS诱导的SCM模型中的作用。在小鼠注射LPS（10mg/kg）诱导SCM模型前，先用LIQ预处理7天。注射LPS 12小时后，采用超声心动图分析评估心脏功能。此后，处死小鼠以收集心脏，分别通过逆转录聚合酶链反应（RT-PCR）、蛋白质免疫印迹法、免疫组织化学和末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）染色分析进行分子和组织病理学检测。使用AMPKα2基因敲除（AMPKα2）小鼠来阐明LIQ的作用机制。用或不用LPS处理的新生大鼠心肌细胞（NRCMs）用于进一步研究LIQ的作用和机制。基于LPS处理导致的左室射血分数（EF）、左室短轴缩短率（FS）、左室舒张末期内径（LVEDs）、心率、最大dp/dt和最小dp/dt的恢复，给予LIQ可减轻LPS诱导的小鼠心脏功能障碍并降低死亡率。LIQ治疗还降低了肿瘤坏死因子α（TNFα）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）的mRNA表达，抑制了炎性细胞迁移，抑制了心脏氧化应激和细胞凋亡，并改善了代谢。机制上，LIQ增强了AMP激活的蛋白激酶α2（AMPKα2）的磷酸化，并降低了哺乳动物雷帕霉素靶蛋白复合物1（mTORC1）、IκBα和核因子κB/p65的磷酸化。重要的是，在AMPKα2基因敲除模型中未观察到LIQ的有益作用，在用AMPK抑制剂抑制AMPK活性后的模型中也未观察到。我们已经证明，LIQ在LPS诱导的SCM模型中发挥保护作用。LIQ通过调节AMPKα2依赖性信号通路减轻炎症、氧化应激、细胞凋亡和代谢改变。因此，LIQ可能是SCM治疗的一种潜在治疗方法或辅助药物。
