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心衰宁制剂通过调节肠道菌群改善阿霉素诱导的心力衰竭大鼠心脏损伤。

Xinshuaining preparation ameliorates doxorubicin-induced cardiac injury in heart failure rats by regulating gut microbiota.

作者信息

Nie Qian, Zhao Jue, Haseeb Sattar, Deng Siwei, Zhang Xin, Wang Rui, Luo Xu, Xie Wen

机构信息

Department of Cardiology, Hospital of Chengdu University of Traditional Chinese Medicine, No.39-41, Shierqiao Road, Jinniu District, Chengdu, 610075, China.

Chengdu University of Traditional Chinese Medicine, Chengdu, China.

出版信息

Drug Deliv Transl Res. 2025 May 26. doi: 10.1007/s13346-025-01879-9.

Abstract

Heart failure (HF) has a serious impact on patients' lives and health. Gut microbiota plays an important role in the development of HF. Xinshuaining (XSN) preparation has a therapeutic effect on the HF. However, the mechanism of action of XSN in HF is still unclear. Our study aimed to explore the possible function and mechanism of XSN on HF induced by doxorubicin (DOX) in rats. DOX-induced HF rat models were prepared, grouped and treated. The ultrasound indexes of rat heart were measured before sampling, and the indexes of cardiac pathology, fibrosis degree, gut microbiota and metabolites were detected by ELISA, HE staining, Masson staining, immunohistochemistry, 16SrDNA sequencing, liquid chromatography-mass spectrometry (LC/MS) after sampling. XSN can significantly improve the cardiac function of HF rats, including increasing LVEF, LVFS, decreasing LVESD, LVESV, LVEDV levels, and at the same time, XSN can also reduce the heart weight index, reduce the cardiac histopathological damage and fibrosis. In addition, XSN can regulate the abundance and function of gut microbiota, inhibit the level of TMAO, and regulate plasma metabolites in HF rats. In conclusions, XSN improves cardiac function and delays the process of cardiac fibrosis in HF rats, and its mechanism may be related to the regulation of gut microbiota and metabolites.

摘要

心力衰竭(HF)对患者的生活和健康有严重影响。肠道微生物群在HF的发展中起重要作用。心衰宁(XSN)制剂对HF有治疗作用。然而,XSN在HF中的作用机制仍不清楚。我们的研究旨在探讨XSN对阿霉素(DOX)诱导的大鼠HF的可能作用及机制。制备DOX诱导的HF大鼠模型,进行分组和治疗。在取样前测量大鼠心脏的超声指标,取样后通过ELISA、HE染色、Masson染色、免疫组织化学、16SrDNA测序、液相色谱 - 质谱联用(LC/MS)检测心脏病理学指标、纤维化程度、肠道微生物群和代谢产物指标。XSN可显著改善HF大鼠的心功能,包括提高左室射血分数(LVEF)、左室短轴缩短率(LVFS),降低左室舒张末期内径(LVESD)、左室舒张末期容积(LVESV)、左室收缩末期容积(LVEDV)水平,同时,XSN还可降低心脏重量指数,减轻心脏组织病理学损伤和纤维化。此外,XSN可调节肠道微生物群的丰度和功能,抑制氧化三甲胺(TMAO)水平,并调节HF大鼠的血浆代谢产物。总之,XSN改善HF大鼠的心功能并延缓心脏纤维化进程,其机制可能与调节肠道微生物群和代谢产物有关。

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