Chen Lina, Guo Yuan, Qu Shuiqing, Li Kai, Yang Ting, Yang Yuanmin, Zheng Zhongyuan, Liu Hui, Wang Xi, Deng Shuoqiu, Zhang Yu, Zhu Xiaoxin, Li Yujie
Artemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
Front Pharmacol. 2021 Mar 8;12:619311. doi: 10.3389/fphar.2021.619311. eCollection 2021.
Ultrafine particulate matter (UFPM) induces oxidative stress (OS) and is considered to be a risk factor of myocardial ischemia (MI). Shengmai formula (SMF) is a traditional Chinese medicine with antioxidant properties and has been used to treat cardiovascular diseases for a long time. The aim of this study was to explore the protective role of SMF and the mechanism by which it prevents myocardial injury in UFPM-exposed rats with MI. An MI rat model was established. Animals were randomly divided into five groups: sham, UFPM + MI, SMF (1.08 mg/kg⋅d) + UFPM + MI, SMF (2.16 mg/kg⋅d) + UFPM + MI, and SMF (4.32 mg/kg⋅d) + UFPM + MI. SMF or saline was administrated 7 days before UFPM instillation (100 μg/kg), followed by 24 h of ischemia. Physiological and biochemical parameters were measured, and histopathological examinations were conducted to evaluate myocardial damage. We also explored the potential mechanism of the protective role of SMF using a system pharmacology approach and an myoblast cell model with small molecule inhibitors. UFPM produced myocardial injuries on myocardial infarct size; serum levels of LDH, CK-MB, and cardiac troponin; and OS responses in the rats with MI. Pretreatment with SMF significantly attenuated these damages reversing the biomarkers. SMF also improved histopathology induced by UFPM and significantly altered the PI3K/AKT/MAPK and OS signaling pathways. The expression patterns of , , and in the UFPM model group were reversed in the SMF-treated group. In studies, SMF attenuated UFPM-induced reactive oxygen species production, mitochondrial damage, and OS responses. The PI3K/AKT/p38 MAPK/Nrf2 pathway was significantly changed in the SMF group compared with that in the UFPM group, whereas opposite results were obtained for pathway inhibition. These findings indicate that SMF prevents OS responses and exerts beneficial effects against myocardial injury induced by UFPM + MI in rats. Furthermore, the PI3K/AKT/p38 MAPK/Nrf2 signaling pathway might be involved in the protective effects of SMF.
超细颗粒物（UFPM）可诱导氧化应激（OS），被认为是心肌缺血（MI）的一个危险因素。生脉方（SMF）是一种具有抗氧化特性的中药，长期以来一直用于治疗心血管疾病。本研究的目的是探讨SMF在暴露于UFPM的MI大鼠中预防心肌损伤的保护作用及其机制。建立了MI大鼠模型。动物被随机分为五组：假手术组、UFPM + MI组、SMF（1.08 mg/kg·d）+ UFPM + MI组、SMF（2.16 mg/kg·d）+ UFPM + MI组和SMF（4.32 mg/kg·d）+ UFPM + MI组。在滴注UFPM（100 μg/kg）前7天给予SMF或生理盐水，随后进行24小时缺血。测量生理和生化参数，并进行组织病理学检查以评估心肌损伤。我们还使用系统药理学方法和带有小分子抑制剂的成肌细胞模型探索了SMF保护作用的潜在机制。UFPM对MI大鼠的心肌梗死面积、血清乳酸脱氢酶（LDH）、肌酸激酶同工酶（CK-MB）和心肌肌钙蛋白水平以及OS反应均产生了心肌损伤。SMF预处理显著减轻了这些损伤，使生物标志物恢复正常。SMF还改善了UFPM诱导的组织病理学变化，并显著改变了PI3K/AKT/MAPK和OS信号通路。在SMF治疗组中，UFPM模型组中相关基因的表达模式发生了逆转。在细胞研究中，SMF减轻了UFPM诱导的活性氧生成、线粒体损伤和OS反应。与UFPM组相比，SMF组中PI3K/AKT/p38 MAPK/Nrf2通路发生了显著变化，而通路抑制则得到相反的结果。这些发现表明，SMF可预防OS反应，并对UFPM + MI诱导的大鼠心肌损伤发挥有益作用。此外，PI3K/AKT/p38 MAPK/Nrf2信号通路可能参与了SMF的保护作用。
