School of Anesthesiology, Shandong Provincial Medicine and Health Key Laboratory of Clinical Anesthesia, Weifang Medical University, Weifang 261053, China.
School of Anesthesiology, Shandong Provincial Medicine and Health Key Laboratory of Clinical Anesthesia, Weifang Medical University, Weifang 261053, China.
Biomed Pharmacother. 2022 Jun;150:113014. doi: 10.1016/j.biopha.2022.113014. Epub 2022 Apr 30.
Propofol (PPF) has a protective effect on myocardial ischemia-reperfusion (I/R) injury (MIRI). The purpose of this study was to investigate whether the myocardial protective effect of propofol is related to the inhibition of mast cell degranulation and explore the possible mechanisms involved. Our in vivo results showed that compared with the sham group, cardiac function, infarct size, histopathological damage, apoptosis, and markers of myocardial necrosis were significantly increased in the ischemia-reperfusion group, and propofol pretreatment alleviated these effects. In the coculture system, propofol-treated mast cells reduced their tryptase activity, resulting in cardiomyocyte protective effects, such as decreased apoptosis of cardiomyocytes and decreased expression of myocardial necrosis markers. Finally, experimental results in vitro revealed that thapsigargin (TG) can increase mast cell degranulation, tryptase release, calcium ion concentration, and the expression of STIM1 and Orai1 induced by H/R, but propofol pretreatment can partially reverse the above effects. These results suggested that the cardioprotective effect of propofol is achieved in part by inhibiting calcium influx through store-operated Ca channels (SOCs) and thus alleviating mast cell degranulation.
异丙酚(PPF)对心肌缺血再灌注(I/R)损伤(MIRI)具有保护作用。本研究旨在探讨异丙酚的心肌保护作用是否与抑制肥大细胞脱颗粒有关,并探讨其可能的机制。我们的体内研究结果表明,与假手术组相比,缺血再灌注组的心脏功能、梗死面积、组织病理学损伤、细胞凋亡和心肌坏死标志物均显著增加,异丙酚预处理可减轻这些作用。在共培养系统中,经异丙酚处理的肥大细胞降低了其胰蛋白酶活性,从而发挥了对心肌细胞的保护作用,如减少心肌细胞凋亡和降低心肌坏死标志物的表达。最后,体外实验结果表明,他普西龙(TG)可增加肥大细胞脱颗粒、胰蛋白酶释放、钙离子浓度以及 H/R 诱导的 STIM1 和 Orai1 的表达,而异丙酚预处理可部分逆转上述作用。这些结果表明,异丙酚的心脏保护作用部分是通过抑制钙内流通过储存操作钙通道(SOCs)来实现的,从而减轻肥大细胞脱颗粒。