【摘要】 目的 探讨左西孟旦对大鼠离体心肌停灌/再灌注过程中环磷酸鸟苷-腺苷酸合成酶/干扰素基因刺激因子（cGAS-STING）信号通路的影响。方法 将大鼠分为持续灌注组（CO组）、停灌/再灌注组（SR组）、停灌/再灌注+左西孟旦组（SR-L组）及停灌/再灌注+左西孟旦+STING激活剂DMXAA组（SR-LD组）。分别在平衡灌注末（T0）、再灌注30 min（T₁）和再灌注60 min（T₂）时记录心率（HR）、左室舒张末压（LVEDP）、左室发展压（LVDP）、左室内压最大上升速率(+dp/dt_max)和左室内压最大下降速率(-dp/dt_max)和再灌注心律失常评分分数。Western blot检测cGAS-STING信号通路及自噬相关蛋白表达，氯化三苯基四氮唑（TTC）染色法测定心肌梗死面积百分比。结果 与CO组相比，SR组T₁、T₂时HR、LVDP、+dp/dt_max和-dp/dt_max降低，LVEDP升高，再灌注心律失常评分增加，心肌梗死面积百分比增加，心肌组织cGAS、STING蛋白表达升高，LC3Ⅱ/Ⅰ比值升高，p62降低（P<0.05）;与SR组比较，SR-L组心功能指标改善，心肌组织cGAS、STING蛋白表达下调，LC3Ⅱ/Ⅰ比值降低，p62升高（P<0.05）;与SR-L相比，SR-LD组逆转了左西孟旦对心肌损伤的保护作用。结论 左西孟旦可能通过抑制cGAS-STING信号通路及下调心肌细胞自噬，改善心功能，减少心肌梗死面积，从而发挥心肌保护作用。更多还原

【Abstract】 Objective To investigate the effect of levosimendan on the cyclic guanosine monophosphate-adenosin monophosphate synthase-interferon gene stimulating factor（cGAS-STING） signaling pathway during suspension-reperfusion in isolated rat myocardium. Methods The rats were divided into four groups（n=12） using random number table: continuous perfusion group（CO group）,suspension-reperfusion group（SR group）,suspension-reperfusion+levosimendan group（SR-L group）, and suspension-reperfusion+levosimendan+STING activator: DMXAA group（SR-LD group）. Heart rate（HR）, left ventricular end-diastolic pressure（LVEDP）, left ventricular developmental pressure（LVDP）, maximum rate of increase in left ventricular pressure(+dp/dt_max) and maximum rate of decrease in left ventricular pressure（-dp/dtmax）, and Reperfusion Arrhythmia scores were recorded at the end of equilibrium perfusion（T0）, 30 min of reperfusion（T1）, and 60 min of reperfusion（T2） respectively. Western blot was used to detect cGAS-STING signaling pathway and autophagy-related protein expression. The size of myocardial infarction was measured by using triphenyl tetrazolium chloride（TTC）.Results Compared with CO group, SR group had decreased HR, LVDP, +dp/dt_max, and-dp/dt_max at T1 and T2, increase of LVEDP,Reperfusion Arrhythmia score, percentage of myocardial infarcted area, expression of myocardial tissue cGAS and STING proteins and increased LC3 Ⅱ/Ⅰ ratio, while p62 decreased（P<0.05）; compared with SR group, SR-L group cardiac function indexes improved, myocardial tissue cGAS, STING protein expression was down-regulated, LC3 Ⅱ/Ⅰ ratio was decreased, and p62 was elevated（P<0.05）; SR-LD group reversed the improvement of myocardial injury by levosimendan compared with SR-L. Conclusions Levosimendan may protect myocardial tissue by inhibiting the cGAS-STING signaling pathway, down-regulating cardiomyocyte autophagy and reducing myocardial infarction size, so to improve cardial function.更多还原