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董艳欣通过抑制中性粒细胞浸润和半胱天冬酶-1 活性改善急性心肌缺血再灌注损伤。

Dunye Guanxinning Improves Acute Myocardial Ischemia-Reperfusion Injury by Inhibiting Neutrophil Infiltration and Caspase-1 Activity.

机构信息

Institute of Interdisciplinary Medical Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

出版信息

Mediators Inflamm. 2018 Feb 20;2018:4608017. doi: 10.1155/2018/4608017. eCollection 2018.

Abstract

Acute myocardial infarction is the most serious manifestation of cardiovascular disease, and it is a life-threatening condition. Dunye Guanxinning (DG) is a protective traditional Chinese patent herbal medicine with high clinical efficacy and suitable for the treatment of myocardial infarction. However, the mechanism through which it is beneficial is unclear. In this study, we hypothesized that DG improves acute myocardial ischemia-reperfusion injury by inhibiting neutrophil infiltration and caspase-1 activity. We found that DG administration decreased infarct size and cardiomyocyte apoptosis and improved left ventricular ejection fraction, fractional shortening, end-systolic volume index, end-systolic diameter, and carotid arterial blood flow output in rats. DG administration also improved hemorheological parameters, myocardial damage biomarkers, and oxidative stress indexes. The findings showed that DG administration inhibited neutrophil infiltration and reduced the serum interleukin-1 beta (IL-1) level and myocardial IL-1 maturation. Moreover, DG administration inhibited caspase-1 activity and activated adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in rat hearts. These results suggested that DG administration inhibits inflammasome activity and IL-1 release through the AMPK pathway. Our findings support the clinical efficacy of DG and partially reveal its mechanism, which is beneficial for understanding the therapeutic effects of this protective traditional Chinese patent drug.

摘要

急性心肌梗死是心血管疾病最严重的表现形式,是一种危及生命的疾病。丹叶冠心宁是一种具有高临床疗效的保护传统中药专利药,适用于治疗心肌梗死。然而,其有益作用的机制尚不清楚。在本研究中,我们假设 DG 通过抑制中性粒细胞浸润和半胱天冬酶-1 活性来改善急性心肌缺血再灌注损伤。我们发现,DG 给药可减少大鼠的梗死面积和心肌细胞凋亡,改善左心室射血分数、缩短分数、收缩末期容积指数、收缩末期直径和颈动脉血流输出。DG 给药还改善了血液流变学参数、心肌损伤生物标志物和氧化应激指标。研究结果表明,DG 给药抑制中性粒细胞浸润,降低血清白细胞介素-1β(IL-1)水平和心肌 IL-1 成熟。此外,DG 给药抑制半胱天冬酶-1 活性并激活大鼠心脏中的腺苷单磷酸激活蛋白激酶(AMPK)磷酸化。这些结果表明,DG 给药通过 AMPK 通路抑制炎症小体活性和 IL-1 释放。我们的研究结果支持 DG 的临床疗效,并部分揭示了其机制,这有助于理解这种保护传统中药专利药的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d61/5838499/989122177e15/MI2018-4608017.001.jpg

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