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五味子甲素通过调节 PI3K-AKT/Nrf2/ARE 和 TLR4/MAPK/NF-κB 通路减轻氧化应激和炎症对异丙肾上腺素诱导的大鼠急性心肌梗死的心脏保护作用。

Cardioprotective effects of Schisantherin A against isoproterenol-induced acute myocardial infarction through amelioration of oxidative stress and inflammation via modulation of PI3K-AKT/Nrf2/ARE and TLR4/MAPK/NF-κB pathways in rats.

机构信息

Department of Cardiovascular Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China.

Department of Cardiovascular Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

出版信息

BMC Complement Med Ther. 2023 Aug 4;23(1):277. doi: 10.1186/s12906-023-04081-x.

DOI:10.1186/s12906-023-04081-x
PMID:37542250
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10401759/
Abstract

BACKGROUND AND AIMS

The scientific community is concerned about cardiovascular disease mortality and morbidity, especially myocardial infarction (MI). Schisantherin A (SCA), a dibenzocyclooctadiene lignan monomer found in S. chinensis fruits has cardiovascular advantages such as increasing NO production in isolated rat thoracic aorta and reducing heart damage caused by ischemia-reperfusion (I/R) through decreasing apoptosis. The present study was undertaken to explore the potential effects of SCA on ISO-induced myocardial infarction in rats.

METHODS

Rats were randomly allocated to four groups: control; ISO-treated, and two additional groups of ISO + SCA (5 or 10 mg/kg body weight). All SCA-treated groups were administered with SCA for 20 days and all ISO groups were challenged with ISO on days 19 and 20.

RESULTS

SCA significantly attenuated ISO-induced rise in heart/body weight ratio, myocardial infarct size, and cardiac functional biomarkers (CK-MB, cTnI and BNP). SCA pre- and co-treatment resulted in a significant reduction in oxidative stress (via MDA, NO and GSH and increased activities of SOD, CAT and GPx) and inflammation (via decreased levels of TNF-α, IL-6 and IL-1β) markers when compared to the same levels in cardiac tissue of ISO-treated rats. This study also showed that SCA protects ISO-induced oxidative stress and inflammation by activating the PI3K-AKT/Nrf2/ARE pathway and suppressing TLR4/MAPK/NF-κB pathways. Furthermore, SCA treatment protected histopathological alterations observed in only ISO-treated cardiac transverse sections of rats.

CONCLUSION

In conclusion, the findings of this study suggest that SCA protects against cardiac injury in the ISO-induced MI model of rats.

摘要

背景与目的

科学界关注心血管疾病的死亡率和发病率,尤其是心肌梗死(MI)。五味子甲素(SCA)是从五味子果实中分离出的二苯并环辛二烯木脂素单体,具有增加离体大鼠胸主动脉一氧化氮(NO)生成和减少缺血再灌注(I/R)引起的心脏损伤等心血管优势,通过减少细胞凋亡。本研究旨在探讨 SCA 对 ISO 诱导的大鼠心肌梗死的潜在作用。

方法

大鼠随机分为四组:对照组;ISO 处理组,以及另外两组 ISO+SCA(5 或 10mg/kg 体重)。所有 SCA 处理组均给予 SCA 治疗 20 天,所有 ISO 组在第 19 天和第 20 天接受 ISO 挑战。

结果

SCA 显著减轻 ISO 诱导的心脏/体重比升高、心肌梗死面积和心脏功能生物标志物(CK-MB、cTnI 和 BNP)升高。与 ISO 处理大鼠心脏组织中的相同水平相比,SCA 预处理和共同处理导致氧化应激(通过 MDA、NO 和 GSH 降低,SOD、CAT 和 GPx 活性增加)和炎症(通过降低 TNF-α、IL-6 和 IL-1β 水平)标志物显著降低。本研究还表明,SCA 通过激活 PI3K-AKT/Nrf2/ARE 通路和抑制 TLR4/MAPK/NF-κB 通路来保护 ISO 诱导的氧化应激和炎症。此外,SCA 治疗可保护仅在 ISO 处理大鼠心脏横切片中观察到的组织病理学改变。

结论

综上所述,本研究结果表明,SCA 可防止 ISO 诱导的大鼠心肌梗死模型中的心脏损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0239/10401759/f5e260a177a9/12906_2023_4081_Fig8_HTML.jpg
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