替格瑞洛在小鼠脓毒症模型中通过腺苷依赖途径减轻脓毒症诱导的心肌损伤。

IF 1.2 4区 医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL
Shengxing Tang, Cong Fu, Qiancheng Xu, Wenjun Guo, Yuhan Cao
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引用次数: 4

摘要

目的:本研究的目的是确定替格瑞洛这一经典抗血小板药物对败血症性心肌损伤是否有治疗作用。方法:C57BL6J小鼠口服替格瑞洛(10、25、50 mg/kg) 7 d后行盲肠结扎穿刺(CLP)。在CLP前2小时给予腺苷受体拮抗剂(CGS15943)。24h后,采用心脏超声心动图检测心功能,采集心脏及血液。采用苏木精伊红(HE)染色和末端脱氧核苷酸转移酶dUTP缺口端标记(TUNEL)染色观察病理变化和心肌细胞凋亡情况。测定血浆TNF-α、IL-6、腺苷浓度及心肌组织TNF-α、IL-6水平。进行生存分析。Western blot检测心肌组织中信号蛋白的表达。结果:HE和TUNEL染色显示替格瑞洛组炎症细胞浸润减少,心肌细胞凋亡减少。心脏超声心动图显示替格瑞洛组心脏功能保持正常。替格瑞洛组血浆TNF-α、IL-6及心肌组织中TNF-α、IL-6的相对表达量均显著降低。替格瑞洛组血浆腺苷水平明显升高。腺苷受体拮抗剂明显阻断替格瑞洛的保护作用。替格瑞洛降低了脓毒症小鼠的死亡率,这种降低被腺苷受体拮抗剂阻断。Western blot结果显示替格瑞洛激活了AKT和mTOR的磷酸化。腺苷受体拮抗剂抑制AKT和mTOR的激活。结论:替格瑞洛的保护作用依赖于腺苷受体的激活,下游上调AKT和mTOR的磷酸化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Ticagrelor alleviates sepsis-induced myocardial injury via an adenosine-dependent pathway in a mouse sepsis model.

Purpose: The purpose of this study was to determine whether ticagrelor, a classic anti-platelet drug, has a therapeutic effect on sepsis-induced myocardial injury.

Methods: The C57BL6J mice received oral ticagrelor (10, 25 and 50 mg/kg) for seven days after which cecum ligation and puncture (CLP) were performed. An adenosine-receptor antagonist (CGS15943) was administered two hours before CLP. After 24 h, cardiac function was measured using cardiac echocardiography, then the heart and blood were collected. Hematoxylin and eosin (HE) staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL staining) were used to observe pathological changes and cardiomyocyte apoptosis. Plasma concentration of TNF-α, IL-6 and adenosine and myocardial tissue levels of TNF-α and IL-6 were determined. Survival analysis was performed. Western blot was used to determine the expression of a signalling protein in the myocardial tissue.

Results: The HE and TUNEL staining showed less inflammatory cell infiltration and less cardiomyocyte apoptosis in the ticagrelor group. Cardiac echocardiography showed preserved heart function in the ticagrelor group. Plasma TNF-α, IL-6 and relative expression of TNF-α and IL-6 in myocardial tissue were significantly lower in the ticagrelor group. Plasma adenosine levels were significantly higher in the ticagrelor group. Adenosine-receptor antagonists significantly blocked the protective effect of ticagrelor. Ticagrelor reduced the mortality of sepsis mice, and this reduction was blocked by the adenosine-receptor antagonist. Western blot showed that ticagrelor activated the phosphorylation of AKT and mTOR. Adenosine-receptor antagonists inhibited the activation of AKT and mTOR.

Conclusion: The protective effect of ticagrelor was dependent on adenosine-receptor activation, with downstream upregulation of phosphorylation of AKT and mTOR.

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来源期刊
Clinical and Investigative Medicine
Clinical and Investigative Medicine 医学-医学:研究与实验
CiteScore
1.50
自引率
12.50%
发文量
18
审稿时长
>12 weeks
期刊介绍: Clinical and Investigative Medicine (CIM), publishes original work in the field of Clinical Investigation. Original work includes clinical or laboratory investigations and clinical reports. Reviews include information for Continuing Medical Education (CME), narrative review articles, systematic reviews, and meta-analyses.
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