Chen Yu, Peng Lei, Shi Shaoqing, Guo Gang, Wen Heling
Department of Cardiology, Sichuan Academy of Medical Science &Sichuan Provincial People's Hospital, Chengdu, China.
Department of Nephrology, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Chengdu, China.
J Cell Mol Med. 2021 Jul;25(13):6403-6416. doi: 10.1111/jcmm.16620. Epub 2021 May 24.
Myocardial infarction (MI) is the most common heart disease, and also, it is one of the leading causes of death from cardiovascular disease. It is well known that MI causes additional injury during blood flow restoration in ischaemic myocardium. Boeravinone B (BB) is a well-known antioxidant and anti-inflammatory drug. We investigated the cardioprotective effect of BB drug against isoproterenol (ISO)-induced MI in rats in this experimental study, along with we analysed its underlying mechanism. Adult Sprague Dawley (SD) rats were treated subcutaneously with ISO (45 mg/kg), then divided into groups and then given BB drug was administered orally. The cardioprotective effect of BB on ISO-induced MI rats was analysed by estimating the heart injury markers, antioxidant pro-inflammatory cytokines and inflammatory parameters. We also detected quantified expression of inflammation and apoptosis-related marker protein family. We estimated the effect of BB drug on GUT microbiota in ISO-induced MI rats and scrutinized the histopathological variations in heart tissues. BB treatment significantly (P < .001) diminished the level of heart markers such as lactate dehydrogenase (LDH), troponin (TnT), creatine kinase (CK) and creatine kinase isoenzymes MB (CK-MB). BB treatment also altered the antioxidant parameters and reduced the pro-inflammatory cytokines in the serum and tissues. Additionally, the histopathological aspects demonstrated that the pathological changes observed in the heart tissue of the ISO group rats were suppressed by the BB treatment to varying degrees. Furthermore, the expressions of caspase-3, p53, caspase-9, Bax, interleukin-6 (IL-6), cytochrome C, neutrophil gelatinase-associated lipocalin (NGAL), tumour necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB) and interleukin-1β (IL-1β) in the heart tissue were down-regulated whereas the Bcl-2 expression seemed to be enhanced. BB treatment not only alleviated ISO-induced gut dysbiosis by its enhanced specified Firmicutesto-Bacteroidetes (F/B) ratio but also maintained the relative abundance of major bacteria such as Clostridium IV, Butyricicoccus, Clostridium XIVs, Akkermansia and Roseburia. Collectively, our findings showed that the BB drug acted against myocardial infraction and prevented the damage by reducing the oxidative stress and controlling the inflammatory pathways, and gut microbiota.
心肌梗死（MI）是最常见的心脏病，也是心血管疾病导致死亡的主要原因之一。众所周知，心肌梗死在缺血心肌血流恢复过程中会造成额外损伤。波瑞黄酮B（BB）是一种著名的抗氧化和抗炎药物。在本实验研究中，我们研究了BB药物对异丙肾上腺素（ISO）诱导的大鼠心肌梗死的心脏保护作用，并分析了其潜在机制。成年Sprague Dawley（SD）大鼠皮下注射ISO（45mg/kg），然后分组并口服给予BB药物。通过评估心脏损伤标志物、抗氧化促炎细胞因子和炎症参数，分析BB对ISO诱导的心肌梗死大鼠的心脏保护作用。我们还检测了炎症和凋亡相关标志物蛋白家族的定量表达。我们评估了BB药物对ISO诱导的心肌梗死大鼠肠道微生物群的影响，并仔细观察了心脏组织的组织病理学变化。BB治疗显著（P<0.001）降低了乳酸脱氢酶（LDH）、肌钙蛋白（TnT）、肌酸激酶（CK）和肌酸激酶同工酶MB（CK-MB）等心脏标志物的水平。BB治疗还改变了抗氧化参数，降低了血清和组织中的促炎细胞因子。此外，组织病理学方面表明，BB治疗不同程度地抑制了ISO组大鼠心脏组织中观察到的病理变化。此外，心脏组织中半胱天冬酶-3、p53、半胱天冬酶-9、Bax、白细胞介素-6（IL-6）、细胞色素C、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、肿瘤坏死因子-α（TNF-α）、核因子κB（NF-κB）和白细胞介素-1β（IL-1β）的表达下调，而Bcl-2表达似乎增强。BB治疗不仅通过提高特定的厚壁菌门与拟杆菌门（F/B）比例减轻了ISO诱导的肠道菌群失调，还维持了主要细菌如IV型梭菌、丁酸球菌、XIVs型梭菌、阿克曼氏菌和罗氏菌的相对丰度。总的来说，我们的研究结果表明，BB药物对心肌梗死有作用，并通过降低氧化应激和控制炎症途径以及肠道微生物群来预防损伤。
