Formononetin alleviates no reflow after myocardial ischemia-reperfusion via modulation of gut microbiota to inhibit inflammation

IF 5.2 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
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Abstract

Gut microflora plays an important role in relieving myocardial no-reflow (NR), formononetin (FMN) has potential effects on NR, however, the relationship between this effect and gut microflora remains unclear. This study aimed to evaluate the role of FMN in alleviating NR by regulating gut microflora. We used a myocardial NR rat model to confirm the effect and mechanism of action of FMN in alleviating NR. The rats were randomly divided into sham operation group (Sham), NR group, FMN group and sodium nitroprusside (SNP) group. Thioflavin S staining, Hematoxylin Eosin (HE), myocardial enzyme activity, ultrasonic cardiogram and RT-PCR detection showed that FMN could effectively reduce inflammatory cell infiltration, NR and ischemic area, improve cardiac structure and function and reduce TNF-α and NF-κB gene expression in NR rats. The results of 16S rRNA high-throughput sequencing showed that FMN could increase the abundance of anti-inflammatory bacteria such as Ligilactobacillus, Coprococcus, Blautia and Muribaculaceae and decrease the abundance of pro-inflammatory bacteria such as Treponema in Spirochaetota and Campylobacterota. The correlation between the differential bacteria in the gut microflora(anti-inflammatory bacteria and pro-inflammatory bacteria) and TNF-α and NF-κB, showed that they had a strong correlation. Therefore, the anti-NR mechanism of FMN may be related to increasing the abundance of anti-inflammatory bacteria and reducing the abundance of pro-inflammatory bacteria to inhibit inflammation. This study provides innovative mechanistic insights into the relationship between gut microbiota and myocardial protection, suggesting potential strategy for future treatment of NR.
福莫西汀通过调节肠道微生物群来抑制炎症,从而缓解心肌缺血再灌注后的无回流现象。
肠道微生物菌群在缓解心肌无回流(NR)方面发挥着重要作用,甲萘素(FMN)对NR有潜在影响,但这种影响与肠道微生物菌群之间的关系仍不清楚。本研究旨在评估 FMN 在通过调节肠道微生物菌群减轻 NR 影响方面的作用。我们使用心肌 NR 大鼠模型来证实 FMN 在缓解 NR 方面的作用和作用机制。大鼠随机分为假手术组(Sham)、NR 组、FMN 组和硝普钠组(SNP)。硫黄素 S 染色、苏木精(HE)、心肌酶活性、超声心动图和 RT-PCR 检测结果表明,FMN 能有效减少 NR 大鼠炎症细胞浸润、NR 和缺血面积,改善心脏结构和功能,降低 TNF-α 和 NF-κB 基因表达。16S rRNA高通量测序结果表明,FMN能提高抗炎菌如Ligilaculum、Coprococcus、Blautia和Muribaculaceae的丰度,降低促炎菌如Treponema in Spirochaetota和Campylobacterota的丰度。肠道微生物区系中的不同细菌(抗炎细菌和促炎细菌)与 TNF-α 和 NF-κB 的相关性表明,它们之间有很强的相关性。因此,FMN 的抗 NR 机制可能与增加抗炎细菌的数量和减少促炎细菌的数量以抑制炎症有关。这项研究为肠道微生物群与心肌保护之间的关系提供了创新性的机制见解,为未来治疗 NR 提出了潜在的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Life sciences
Life sciences 医学-药学
CiteScore
12.20
自引率
1.60%
发文量
841
审稿时长
6 months
期刊介绍: Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.
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