Purpose: Coronary microembolization (CME) can cause myocardial inflammation, apoptosis and progressive cardiac dysfunction. On the other hand, breviscapine exerts a significant cardioprotective effect in many cardiac diseases although its role and the potential mechanisms in CME remain unclear. Therefore, the present study aimed to ascertain whether pretreatment with breviscapine could improve CME-induced myocardial injury by alleviating myocardial inflammation and apoptosis. The possible underlying mechanisms were also explored.
Methods: In this study, 48 Sprague-Dawley (SD) rats were randomly assigned to the CME, CME + breviscapine (CME + BE), CME + breviscapine + LY294002 (CME + BE + LY) and sham groups (12 rats per group). In addition, the CME model was successfully established by injecting 42 μm inert plastic microspheres into the left ventricle of rats. Rats in the CME + BE and CME + BE + LY groups received 40 mg/kg/d of breviscapine for 7 days before inducing CME. Moreover, rats in the CME + BE + LY group were intraperitoneally injected with the phosphoinositide 3-kinase (PI3K) specific inhibitor, LY294002 (10 mg/kg) 30 minutes before CME modeling. 12 h after surgery, the study measured cardiac function, the serum levels of markers of myocardial injury, myocardial inflammation-associated mRNAs and proteins, myocardial apoptosis-associated mRNAs and proteins and conducted myocardial histopathology.
Results: The findings demonstrated that pretreatment with breviscapine alleviated myocardial injury following CME by improving cardiac dysfunction, decreasing the serum levels of markers of myocardial injury, reducing the size of myocardial microinfarct and lowering the cardiomyocyte apoptotic index. More importantly, pretreatment with breviscapine resulted to a decrease in the levels of inflammatory and pro-apoptotic mRNAs and proteins in myocardial tissues and there was an increase in the levels of anti-apoptotic mRNAs and proteins. However, these protective effects were eliminated when breviscapine was combined with LY294002.
Conclusion: The findings from this study indicated that breviscapine may inhibit myocardial inflammation and apoptosis by regulating the PI3K/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway, thereby ameliorating CME-induced cardiac dysfunction and reducing myocardial injury.

Keywords: breviscapine, coronary microembolization, PI3K/Akt/GSK-3β, myocardial inflammation, apoptosis


中文翻译：

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灯盏花素预处理通过激活 PI3K/Akt/GSK-3β 信号通路抑制大鼠冠状动脉微栓塞后的心肌炎症和细胞凋亡

目的：冠状动脉微栓塞术（CME）可引起心肌炎症、细胞凋亡和进行性心功能不全。另一方面，灯盏花素在许多心脏病中发挥显着的心脏保护作用，尽管其在 CME 中的作用和潜在机制仍不清楚。因此，本研究旨在确定灯盏花素预处理是否可以通过减轻心肌炎症和细胞凋亡来改善 CME 诱导的心肌损伤。还探讨了可能的潜在机制。
方法：在这项研究中，48 只 Sprague-Dawley (SD) 大鼠被随机分配到 CME、CME + 灯盏花素 (CME + BE)、CME + 灯盏花素 + LY294002 (CME + BE + LY) 和假手术组（每组 12 只大鼠）。此外，通过向大鼠左心室注射42 μm惰性塑料微球，成功建立CME模型。CME + BE 和 CME + BE + LY 组的大鼠在诱导 CME 前接受 40 mg/kg/d 灯盏花素 7 天。此外，CME + BE + LY 组大鼠在 CME 造模前 30 分钟腹腔注射磷酸肌醇 3-激酶 (PI3K) 特异性抑制剂 LY294002 (10 mg/kg)。手术后 12 小时，该研究测量了心脏功能、心肌损伤标志物、心肌炎症相关 mRNA 和蛋白质的血清水平，
结果：研究结果表明，灯盏花素预处理可通过改善心功能障碍、降低血清心肌损伤标志物水平、缩小心肌微梗死面积和降低心肌细胞凋亡指数来减轻 CME 后的心肌损伤。更重要的是，灯盏花素预处理导致心肌组织中炎症和促凋亡 mRNA 和蛋白质水平降低，抗凋亡 mRNA 和蛋白质水平升高。然而，当灯盏花素与 LY294002 联合使用时，这些保护作用就消失了。
结论：本研究结果表明灯盏花素可通过调节 PI3K/蛋白激酶 B (Akt)/糖原合酶激酶-3β (GSK-3β) 通路抑制心肌炎症和细胞凋亡，从而改善 CME 诱导的心功能不全，减轻心肌损伤。

关键词：灯盏花素，冠状动脉微栓塞，PI3K/Akt/GSK-3β，心肌炎症，细胞凋亡