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丹红注射液对大鼠心肌梗死的心脏保护作用关键由微小RNA发挥作用。

Cardioprotective Effect of Danhong Injection against Myocardial Infarction in Rats Is Critically Contributed by MicroRNAs.

作者信息

Chen Jingrui, Wei Jing, Orgah John, Zhu Yan, Ni Jingyu, Li Lingyan, Zhang Han, Gao Xiumei, Fan Guanwei

机构信息

First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

出版信息

Evid Based Complement Alternat Med. 2019 Aug 26;2019:4538985. doi: 10.1155/2019/4538985. eCollection 2019.

Abstract

BACKGROUND

Danhong injection (DHI) has been mainly used for the treatment of myocardial infarction, atherosclerosis, and coronary heart disease in clinical practice. Our previous studies have shown that DHI improves ventricular remodeling and preserves cardiac function in rats with myocardial infarction (MI). In this study, we focused on the potential mechanism of DHI in protecting cardiac function in MI rats.

METHODS

Sprague-Dawley rats were subjected to ligation of the left anterior descending coronary artery (LAD) to prepare a myocardial infarction (MI) model. After 14 day DHI intervention, cardiac function was measured by echocardiography and myocardial fibrosis was assessed by Masson staining. Differentiated miRNAs were screened using rat immunopathology miScript miRNA PCR arrays, and their results were verified by RT-PCR, immunofluorescence, and immunoblotting.

RESULTS

DHI treatment significantly reduced infarct size and improved cardiac function and hemodynamics in MI rats by echocardiography and morphology. miRNA PCR array results showed that DHI reversed 25 miRNAs known to be associated with inflammation and apoptosis. Moreover, the expression of inflammatory factors TNF-, IL-1, and IL-6 was significantly reduced in the treated DHI group. Mechanistically, DHI downregulated the inflammatory transcription factor NF-B (as reflected by inhibition of NF-B p65 nuclear translocation and phosphorylation of the IB).

CONCLUSIONS

DHI is effective in mitigating inflammation associated with MI by preventing NF-B nuclear translocation and regulating miRNAs, thereby improving cardiac function in myocardial infarction rats.

摘要

背景

丹红注射液(DHI)在临床实践中主要用于治疗心肌梗死、动脉粥样硬化和冠心病。我们之前的研究表明,DHI可改善心肌梗死(MI)大鼠的心室重构并保留心脏功能。在本研究中,我们聚焦于DHI保护MI大鼠心脏功能的潜在机制。

方法

将Sprague-Dawley大鼠进行左冠状动脉前降支结扎(LAD)以制备心肌梗死(MI)模型。经过14天的DHI干预后,通过超声心动图测量心脏功能,并通过Masson染色评估心肌纤维化。使用大鼠免疫病理学miScript miRNA PCR阵列筛选差异miRNA,并通过RT-PCR、免疫荧光和免疫印迹验证其结果。

结果

通过超声心动图和形态学观察,DHI治疗显著减小了MI大鼠的梗死面积,改善了心脏功能和血流动力学。miRNA PCR阵列结果显示,DHI逆转了25种已知与炎症和凋亡相关的miRNA。此外,在接受DHI治疗的组中,炎症因子TNF-、IL-1和IL-6的表达显著降低。机制上,DHI下调了炎症转录因子NF-κB(表现为抑制NF-κB p65核转位和IκB的磷酸化)。

结论

DHI通过阻止NF-κB核转位和调节miRNA有效减轻与MI相关的炎症,从而改善心肌梗死大鼠的心脏功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b06a/6732666/e5066f89e6b5/ECAM2019-4538985.001.jpg

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