Pretreatment with antiplatelet drugs improves the cardiac function after myocardial infarction without reperfusion in a mouse model.
Pretreatment with antiplatelet drugs improves the cardiac function after myocardial infarction without reperfusion in a mouse model.
复制标题
抗血小板药物预处理可改善心肌梗死后小鼠模型的心功能，无需再灌注
DOI：
10.5603/cj.a2019.0051
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发表时间：
2021
影响因子：
2.9
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Zhang K;Yang W;Zhang M;Sun Y;Zhang T;Liu J;Zhang J
背景再灌注治疗可以改善心肌梗死（MI）后的预后并限制心肌损伤。经皮冠状动脉介入治疗前给予抗血小板药物也证明对急性心肌梗死（AMI）患者有益。然而，许多AMI患者没有接受再灌注治疗，目前尚不清楚他们是否会受益于抗血小板预治疗。方法实验用C57 BL/6小鼠随机分为5组：假手术组、对照组、治疗后组、治疗前组、治疗前后组。在治疗组中灌胃给予乙酰水杨酸（15 mg/kg）、氯吡格雷（11 mg/kg）、替格瑞洛（27 mg/kg）和普拉格雷（1.5 mg/kg）。在MI后第7天，分别使用超声心动图和Masson三色染色评价心脏功能和心脏纤维化。对组织切片进行组织学检查以分级炎性细胞浸润。通过测量凝血酶诱导的血小板聚集来监测血小板抑制。结果治疗前两组患者左室射血分数、左室短轴缩短率较治疗后两组及对照组均有显著改善（P < 0.01）。与治疗后组和对照组相比，在治疗前组中观察到心脏纤维化显著减少（p < 0.01）。与对照组相比，治疗前组炎症细胞浸润明显减少（p < 0.05）。凝血酶诱导的血小板聚集被抗血小板药物显著抑制，但随着暴露于H2 O2而增加。结论在无再灌注治疗的情况下，抗血小板药物预处理可有效改善心肌梗死后的心功能，减少心肌纤维化和炎性细胞浸润，抑制氧化应激诱导的血小板聚集。
Background Reperfusion therapy is known to improve prognosis and limit myocardial damage after myocardial infarction (MI). The administration of antiplatelet drugs prior to percutaneous coronary intervention also proves beneficial to patients with acute MI (AMI). However, a good number of AMI patients do not receive reperfusion therapy, and it is not clear if they would benefit from antiplatelet pre-treatment. Methods Experimental C57BL/6 mice were randomly allocated to five groups: the sham group, control, post-treatment, pre-treatment, and pre- and post-treatment groups. Acetylsalicylic acid (15 mg/kg), clopidogrel (11 mg/kg), ticagrelor (27 mg/kg), and prasugrel (1.5 mg/kg) were intragastrically administered in the treatment groups. On day 7 post MI, cardiac function and cardiac fibrosis were evaluated using echocardiography and Masson’s trichrome staining, respectively. Histopathological examinations were performed on tissue sections to grade inflammatory cell infiltration. Platelet inhibition was monitored by measuring thrombin-induced platelet aggregation. Results Left ventricular ejection fraction and fractional shortening improved significantly (p < 0.01) in the pre-treatment groups when compared to the post-treatment and control groups. A significant (p < 0.01) decrease in cardiac fibrosis was observed in the pre-treatment group, compared with the post-treatment and control groups. Inflammatory cell infiltration significantly decreased in the pre-treatment group compared with the control group (p < 0.05). Thrombin-induced platelet aggregation was significantly inhibited by antiplatelet drugs, but increased with the exposure to H2O2. Conclusions In the absence of reperfusion therapy, pre-treatment with antiplatelet drugs successfully improved cardiac function, reduced cardiac fibrosis and inflammatory cell infiltration, and inhibited oxidative stress-induced platelet aggregation after MI in the mouse model.